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p(HGNC:CHRNA7)

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Entity

Name
CHRNA7
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 17

albuquerque2009 v1.0.0

This file encodes the article Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function by Albuquerque et al, 2009

Nicotinic acetylcholine receptor signalling: roles in Alzheimer's disease and amyloid neuroprotection. v1.0.0

The Nicotinic Acetylcholine Receptor: The Founding Father of the Pentameric Ligand-gated Ion Channel Superfamily v1.0.1

Nicotinic Acetylcholine Receptors and Nicotinic Cholinergic Mechanisms of the Central Nervous System v1.0.0

Neuronal Nicotinic Acetylcholine Receptor Structure and Function and Response to Nicotine v1.0.1

Alzheimer's Disease: Targeting the Cholinergic System v1.0.0

Identification and Characterization of a G Protein-binding Cluster in alpha7 Nicotinic Acetylcholine Receptors v1.0.0

Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment v1.0.1

NACHO Mediates Nicotinic Acetylcholine Receptor Function throughout the Brain v1.0.0

Neural Systems Governed by Nicotinic Acetylcholine Receptors: Emerging Hypotheses v1.0.0

Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications v1.0.0

Nicotinic Receptor Abnormalities of Alzheimer’s Disease: Therapeutic Implications v1.0.0

Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system v1.0.0

This document contains the curation of the review article Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system by Taly et al. 2009

Chaperoning α7 neuronal nicotinic acetylcholine receptors v1.0.0

Neuronal and Extraneuronal Nicotinic Acetylcholine Receptors. v1.0.0

Chronic Anatabine Treatment Reduces Alzheimer ’ s Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD v1.0.0

Caenorhabditis elegans models of tauopathy v1.0.0

In-Edges 135

complex(a(CHEBI:"amyloid-beta polypeptide 42"), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

a(CHEBI:"amyloid-beta polypeptide 42") decreases act(p(HGNC:CHRNA7)) View Subject | View Object

More functional studies reported that while at picomolar concentrations Abeta1-42 activates alpha7 nAChRs ectopically expressed in Xenopus oocytes (123, 126), at nanomolar concentrations it inhibits alpha7 nAChRs present in different preparations (278, 376). The alpha7 nAChR inhibition by Abeta1-42 is noncompetitive with respect to the agonist, is voltage independent, and is therefore likely to be mediated by the interaction of the peptide with a site different from that for ACh on the nAChRs. PubMed:19126755

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a(CHEBI:"kynurenic acid") decreases act(p(HGNC:CHRNA7)) View Subject | View Object

The neuroactive properties of KYNA have long been attributed to the inhibition of NMDA receptors (329). Electrophysiological studies, however, have demonstrated that physiologically relevant concentrations of KYNA block alpha7 nAChR activity noncompetitively and voltage independently (210). PubMed:19126755

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a(CHEBI:"kynurenic acid") regulates act(p(HGNC:CHRNA7)) View Subject | View Object

This constituted the first evidence that in the hippocampus endogenous levels of KYNA are sufficient to directly modulate the activity of alpha7 nAChRs, but not that of NMDA receptors (31). PubMed:19126755

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MeSH
Hippocampus
Text Location
Review

a(CHEBI:"kynurenic acid") regulates act(p(HGNC:CHRNA7)) View Subject | View Object

Acting as an endogenous regulator of the alpha7 nAChR activity, astrocyte-derived KYNA can modulate synaptic transmission, synaptic plasticity, neuronal viability, and neuronal connectivity in different areas of the brain (Fig. 8). PubMed:19126755

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a(CHEBI:"kynurenic acid") decreases act(p(HGNC:CHRNA7)) View Subject | View Object

As illustrated in Figure 8, KYNA-induced reduction of extracellular dopamine levels can be explained by the inhibition of tonically active alpha7 nAChRs in the dopaminergic neurons within the VTA and/or in cortical glutamatergic terminals that synapse onto striatal neurons. VTA dopaminergic neurons represent the major dopaminergic input to the nucleus accumbens. PubMed:19126755

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MeSH
Dopaminergic Neurons
Text Location
Review

a(CHEBI:"kynurenic acid") decreases act(p(HGNC:CHRNA7)) View Subject | View Object

Chronic alpha7 nAChR inhibition in the hippocampus by elevated levels of KYNA can contribute to auditory gating deficits, which appear to be associated with the development of schizophrenia (156). It is also feasible that KYNAinduced inhibition of alpha7 nAChRs contributes to the cognitive impairment observed in patients with AD and schizophrenia (273). PubMed:19126755

Appears in Networks:
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MeSH
Hippocampus
Text Location
Review

a(CHEBI:anandamide) decreases act(p(HGNC:CHRNA7)) View Subject | View Object

Anandamide, a compound originally isolated from porcine brain extracts, is known to interact with canabinoid receptors 1 and 2 in the brain (120, 159). However, anandamide interacts with numerous other receptors, including voltage-gated Ca2+ channels (357), voltage-gated K+ channels (293), 5-HT3 receptors (358), kainate receptors (3), and nAChRs (356). At nanomolar concentrations, anandamine blocks noncompetitively and voltage independently the activation of alpha7 nAChRs ectopically expressed in Xenopus oocytes (356). It also inhibits the activity of alpha4beta2 nAChRs expressed in SH-EP1 cells (443). PubMed:19126755

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Review

a(CHEBI:bupropion) decreases act(p(HGNC:CHRNA7)) View Subject | View Object

Finally, bupropion (16, 294, 433) and UCI-30002 (514) are examples of synthetic compounds that act as noncompetitive inhibitors of different nAChRs, including those made up of the subunits alpha7, alpha4beta2, or alpha3beta4. Both compounds effectively decrease nicotine self-administration in rats (280, 514). Bupropion is presently approved as an adjunct therapy for smoking cessation. PubMed:19126755

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a(CHEBI:nicotine) association act(p(HGNC:CHRNA7)) View Subject | View Object

A principle component of genetic analysis of the contribution of alpha7 and alpha4beta2 nAChRs to the effects of nicotine was reported 15 years ago. The number of alpha-BGT binding sites (presumably alpha7 nAChRs) was shown to be highly correlated with sensitivity to nicotinic-induced seizures (105, 301, 303). PubMed:19126755

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MeSH
Seizures
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Review

a(HBP:"amyloid-beta oligomers") regulates act(p(HGNC:CHRNA7)) View Subject | View Object

However, this appealing scenario is complicated by recent findings that beta-amyloid peptides directly modify alpha7 nAChR function (242, 278). PubMed:19126755

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a(MESH:"Cholinesterase Inhibitors") causesNoChange act(p(HGNC:CHRNA7)) View Subject | View Object

In fact, as described above, AChE inhibitors do not affect alpha7 nAChR-mediated synaptic transmission evoked by low-frequency stimulation of cholinergic fibers in chick ciliary ganglia (522). PubMed:19126755

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Review

a(MESH:"N-(1,2,3,4-tetrahydro-1-naphthyl)-4-nitroaniline") decreases act(p(HGNC:CHRNA7)) View Subject | View Object

Finally, bupropion (16, 294, 433) and UCI-30002 (514) are examples of synthetic compounds that act as noncompetitive inhibitors of different nAChRs, including those made up of the subunits alpha7, alpha4beta2, or alpha3beta4. Both compounds effectively decrease nicotine self-administration in rats (280, 514). Bupropion is presently approved as an adjunct therapy for smoking cessation. PubMed:19126755

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Text Location
Review

a(MESH:Hippocampus) increases p(HGNC:CHRNA7) View Subject | View Object

However, in hippocampal neurons expressing the alpha7, alpha4, and beta2 nAChR subunits, the vast majority of functional nAChRs are pharmacologically identified as being distinctly alpha4beta2 and alpha7 nAChRs (12). PubMed:19126755

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a(MESH:Neurons) association p(HGNC:CHRNA7) View Subject | View Object

For example, while the alpha7 nAChR is primarily a homomeric receptor in neurons (127), combinations of alpha7 nAChR subunits with alpha5, beta2, or beta3 nAChR subunits have been reported to form functional heteromeric receptors in some systems (240, 360, 515). PubMed:19126755

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bp(GO:cognition) positiveCorrelation p(HGNC:CHRNA7) View Subject | View Object

In particular, the association of the alpha7 nAChR gene with a sensory gating deficit that is similar to attention deficits in patients with schizophrenia (157), and the degree of alpha4beta2 nAChR loss and altered alpha7 expresson correlate well with the magnitude of progressive cognitive decline in mild-to-moderate AD patients (46). PubMed:19126755

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Text Location
Review

bp(GO:cognition) association act(p(HGNC:CHRNA7)) View Subject | View Object

Chronic alpha7 nAChR inhibition in the hippocampus by elevated levels of KYNA can contribute to auditory gating deficits, which appear to be associated with the development of schizophrenia (156). It is also feasible that KYNAinduced inhibition of alpha7 nAChRs contributes to the cognitive impairment observed in patients with AD and schizophrenia (273). PubMed:19126755

Appears in Networks:
Annotations
MeSH
Hippocampus
Text Location
Review

complex(a(MESH:methyllycaconitine), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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complex(a(MESH:methyllycaconitine), p(HGNC:CHRNA7)) decreases act(p(HGNC:CHRNA7, loc(MESH:Muscles))) View Subject | View Object

Finally, the alkaloid methyllycaconitine (MLA) emerged as a potent and specific competitive antagonist that inhibits muscle, alpha7-, alpha6-, and alpha3-containing nAChRs (30, 326, 445). The alkaloid is derived from the larkspur (genus Delphinium), which is of great economic interest since estimates of its cost to ranchers in poisoned livestock exceeds many millions of dollars annually. Similar to most nAChR poisons, MLA binds to the receptor agonistbinding site (Fig. 3) in a manner similar to that of alpha-BGT to block agonist binding and receptor activation. PubMed:19126755

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Review

complex(p(HGNC:CHRNA5), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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complex(p(HGNC:CHRNA5), p(HGNC:CHRNA7)) association p(HGNC:CHRNA7) View Subject | View Object

For example, while the alpha7 nAChR is primarily a homomeric receptor in neurons (127), combinations of alpha7 nAChR subunits with alpha5, beta2, or beta3 nAChR subunits have been reported to form functional heteromeric receptors in some systems (240, 360, 515). PubMed:19126755

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Text Location
Review

complex(p(HGNC:CHRNA7), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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complex(p(HGNC:CHRNA7), p(HGNC:CHRNB2)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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complex(p(HGNC:CHRNA7), p(HGNC:CHRNB2)) association p(HGNC:CHRNA7) View Subject | View Object

For example, while the alpha7 nAChR is primarily a homomeric receptor in neurons (127), combinations of alpha7 nAChR subunits with alpha5, beta2, or beta3 nAChR subunits have been reported to form functional heteromeric receptors in some systems (240, 360, 515). PubMed:19126755

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Text Location
Review

complex(p(HGNC:CHRNA7), p(HGNC:CHRNB3)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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complex(p(HGNC:CHRNA7), p(HGNC:CHRNB3)) association p(HGNC:CHRNA7) View Subject | View Object

For example, while the alpha7 nAChR is primarily a homomeric receptor in neurons (127), combinations of alpha7 nAChR subunits with alpha5, beta2, or beta3 nAChR subunits have been reported to form functional heteromeric receptors in some systems (240, 360, 515). PubMed:19126755

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Text Location
Review

composite(a(MESH:"HEK293 Cells"), g(HGNC:CHRNA7)) decreases act(p(HGNC:CHRNA7)) View Subject | View Object

Upon transfection of the cDNA encoding alpha7 nAChR subunits, HEK293 cells reportedly express the corresponding transcripts and even make considerable protein. Yet, the number of functional receptors expressed on the cell surface was low and could vary by three orders of magnitude. PubMed:19126755

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Experimental Factor Ontology (EFO)
HEK293
Text Location
Review

g(HGNC:CHRNA7) increases p(HGNC:CHRNA7) View Subject | View Object

Only two of these cell lines expressed alpha7 nAChRs: GH4C1 cells expressed substantially greater numbers of surface receptors than did SH-EP1 cells, which exhibited poor assembly efficiency. PubMed:19126755

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Experimental Factor Ontology (EFO)
GH4-C1 cell
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Review

composite(p(HGNC:CHRNA4), p(HGNC:CHRNA7), p(HGNC:CHRNB2)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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composite(p(HGNC:CHRNA7), p(HGNC:NGF)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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a(CHEBI:ivermectin) regulates act(p(HGNC:CHRNA7)) View Subject | View Object

Ivermectin is an example of a positive allosteric effector that modifies the pharmacological profile of the α7 nAChR. PubMed:17009926

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path(MESH:"Alzheimer Disease") negativeCorrelation p(HGNC:CHRNA7) View Subject | View Object

In particular, the association of the alpha7 nAChR gene with a sensory gating deficit that is similar to attention deficits in patients with schizophrenia (157), and the degree of alpha4beta2 nAChR loss and altered alpha7 expresson correlate well with the magnitude of progressive cognitive decline in mild-to-moderate AD patients (46). PubMed:19126755

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Annotations
Text Location
Review

path(MESH:"Sensory Gating") association act(p(HGNC:CHRNA7)) View Subject | View Object

Chronic alpha7 nAChR inhibition in the hippocampus by elevated levels of KYNA can contribute to auditory gating deficits, which appear to be associated with the development of schizophrenia (156). It is also feasible that KYNAinduced inhibition of alpha7 nAChRs contributes to the cognitive impairment observed in patients with AD and schizophrenia (273). PubMed:19126755

Appears in Networks:
Annotations
MeSH
Hippocampus
Text Location
Review

a(CHEBI:"amyloid-beta") positiveCorrelation p(HGNC:CHRNA7) View Subject | View Object

In addition, not only have alpha7 nAChRs been found colocalized with plaques (Wang et al., 2000b) but alpha7 and alpha4 subunits are also positively correlated with neurons that accumulate Abeta (Wevers et al., 1999). PubMed:19293145

Appears in Networks:
Annotations
MeSH
Neurons

a(CHEBI:"amyloid-beta") increases act(p(HGNC:CHRNA7)) View Subject | View Object

Curiously, although most studies are in agreement that nAChRs need to be activated to mediate their protective effects, mouse cortical neurons are protected by the alpha7 antagonist methyllycaconitine (Martin et al., 2004), raising the possibility that neuroprotection by alpha7 agonists may be through desensitization rather than activation of this rapidly desensitizing receptor. This would be consistent with the alpha7- dependent activation of intracellular signaling pathways by Abeta (Bell et al., 2004), but the opposite effects on cell survival exerted by Abeta and nicotine means that other mechanisms must be sought, such as ligand-specific coupling to downstream signaling pathways. PubMed:19293145

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a(CHEBI:"amyloid-beta") association p(HGNC:CHRNA7) View Subject | View Object

In contrast, Small et al. (2007) found no displacement of alpha-BTX from SH-SY5Y cells (a cell line very closely related to that used by Wang et al.) by either amyloid or methyllycaconitine. Wang et al. (2000b) also showed similar staining of human AD cortical neurons by alpha7 and Abeta antibodies in double immunofluorescence, suggesting that in human cortical neurons, alpha7 and Abeta are closely associated, although such an approach does not prove direct binding. However another study (Small et al., 2007) showed no displacement of labeled alpha-bungarotoxin from cell lines expressing rat alpha7 nAChRs. PubMed:19293145

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Experimental Factor Ontology (EFO)
SH-SY5Y

a(CHEBI:"amyloid-beta") decreases act(p(HGNC:CHRNA7)) View Subject | View Object

Abeta action on nAChRs depends on subunit composition; it has been reported to block alpha7, transiently potentiate alpha4beta2 before blocking, and to have no action on alpha3beta4 (Pym et al., 2005). However, in contrast to its reported transient enhancement when expressed in oocytes, an inhibition of alpha4beta2 has been reported when expressed in human SH-EP1 cells (Wu et al., 2004). PubMed:19293145

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a(CHEBI:"amyloid-beta") causesNoChange p(HGNC:CHRNA7) View Subject | View Object

Again, despite numerous reports of a block of alpha7, one study indicated that Abeta failed to block alpha7, even though it blocked alpha4beta2, alpha2beta2 and alpha4alpha5beta2 receptors (Lamb et al., 2005). PubMed:19293145

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a(CHEBI:"amyloid-beta") causesNoChange act(p(HGNC:CHRNA7)) View Subject | View Object

It has also been observed that although Abeta inhibits recombinant human and mouse alpha7 nAChRs, transgenic mice overexpressing human Abeta express functional alpha7 nAChRs, and the amplitude of alpha7- mediated currents is no different from that of wild-type mice (Spencer et al., 2006). PubMed:19293145

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a(CHEBI:"amyloid-beta") increases p(HGNC:CHRNA7) View Subject | View Object

Similar effects of Abeta on nAChR expression have been confirmed in studies using cultured cells; Abeta causes a reduced expression of nAChRs in PC12 cells (Guan et al., 2001), and alpha4, alpha3, and alpha7 expression are all increased in cultured rat astrocytes (Xiu et al., 2005). PubMed:19293145

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Annotations
MeSH
Astrocytes

a(CHEBI:donepezil) increases p(HGNC:CHRNA7) View Subject | View Object

Donepezil, which protects cultured rat cortical neurons, when applied for 4 days resulted in an up-regulation of alpha4 and alpha7 nAChRs with the result that donepezil was even more potently protective (Kume et al., 2005). PubMed:19293145

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complex(a(CHEBI:"amyloid-beta"), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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act(a(CHEBI:nicotine)) increases p(HGNC:CHRNA7) View Subject | View Object

The nicotine-induced nAChR up-regulation in human SH-EP1 cells heterologously expressing alpha7 nAChRs is mediated by cAMP and protein kinase C (PKC) (Nuutinen et al., 2006). The effects of long-term nicotine treatment on nAChR expression in rat brain differs for receptors of different subtype composition (most pronounced up-regulation being observed for alpha4beta2 receptors) and for different brain regions (Nguyen et al., 2003). PubMed:19293145

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act(a(MESH:"Vagus Nerve")) increases act(p(HGNC:CHRNA7)) View Subject | View Object

Hepatic vagus nerve activity has recently been shown to protect hepatocytes from Fas-induced apoptosis via activation of alpha7 nAChRs (Hiramoto et al., 2008). Thus, nicotine seems to exert a general pro-survival action not only on neurons but also on non-neuronal cells, suggesting that the protection offered by nicotine against Abeta toxicity may therefore simply be the result of a general pro-survival response. PubMed:19293145

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Annotations
MeSH
Liver

a(MESH:methyllycaconitine) decreases act(p(HGNC:CHRNA7)) View Subject | View Object

Curiously, although most studies are in agreement that nAChRs need to be activated to mediate their protective effects, mouse cortical neurons are protected by the alpha7 antagonist methyllycaconitine (Martin et al., 2004), raising the possibility that neuroprotection by alpha7 agonists may be through desensitization rather than activation of this rapidly desensitizing receptor. This would be consistent with the alpha7- dependent activation of intracellular signaling pathways by Abeta (Bell et al., 2004), but the opposite effects on cell survival exerted by Abeta and nicotine means that other mechanisms must be sought, such as ligand-specific coupling to downstream signaling pathways. PubMed:19293145

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a(MESH:methyllycaconitine) decreases act(p(HGNC:CHRNA7)) View Subject | View Object

In support of this notion, beta-estradiol protects PC12 cells from amyloid toxicity, and this is prevented when alpha7 nAChRs are blocked with methyllycaconitine (Svensson and Nordberg, 1999). PubMed:19293145

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Annotations
Experimental Factor Ontology (EFO)
PC12

bp(GO:"calcium-mediated signaling") association act(p(HGNC:CHRNA7)) View Subject | View Object

Calcium signaling pathways are involved both in the toxic action of Abeta and in the protection against that toxicity offered by nicotinic ligands. Given that alpha7 homomeric nAChRs are much more permeable to calcium ions than are most other nAChRs (Bertrand et al., 1993), it is to be expected that nicotinic neuroprotection mediated by nAChRs, notably alpha7, would depend upon the activation of calcium signaling pathways. ABT-418 is a nicotinic agonist that protects primary rat cortical neurons from glutamate toxicity through its activation of alpha7 nAChRs, and this is blocked when calcium is removed from the extracellular medium (Donnelly-Roberts et al., 1996). PubMed:19293145

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complex(a(CHEBI:methyllycaconitine), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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complex(a(CHEBI:nicotine), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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complex(a(MESH:Bungarotoxins), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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complex(p(FPLX:"PI3K_p85"), p(HGNC:CHRNA7), p(HGNC:FYN)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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complex(p(HGNC:APOE), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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composite(a(CHEBI:"amyloid-beta"), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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composite(p(FPLX:ERK), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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composite(p(FPLX:JNK), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

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p(HGNC:APP, frag("25_35")) increases act(p(HGNC:CHRNA7)) View Subject | View Object

Abeta1–42 activates heterologously expressed nAChRs (Dineley et al., 2002), and Abeta25–35 has been shown to activate non-alpha7 nAChRs in rat basal forebrain neurons (Fu and Jhamandas, 2003) and to evoke a alpha7- mediated calcium increases in presynaptic terminals isolated from rat hippocampus and neocortex (Dougherty et al., 2003). PubMed:19293145

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path(MESH:"Alzheimer Disease") association p(HGNC:CHRNA7) View Subject | View Object

Genetic association studies investigating single nucleotide polymorphisms point to roles for cholinergic signaling components such as the synthetic enzyme ChAT, the inactivating enzyme AChE, and alpha4beta2 nAChRs in AD (Cook et al., 2004, 2005; Vasto et al., 2006). The most vulnerable neurons in AD seem to be those expressing high levels of nAChRs, particularly those containing the alpha7 subunit (D’Andrea and Nagele, 2006), and the numbers of nAChRs as well as some of their associated proteins change in AD (Martin-Ruiz et al., 1999; Gotti et al., 2006; Sabbagh et al., 2006). PubMed:19293145

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path(MESH:"Alzheimer Disease") decreases p(HGNC:CHRNA7) View Subject | View Object

A stereological approach, in which specific, identified regions of cortex were excised as a by-product of therapeutic surgery, revealed an approximately 50% decrease in the number of alpha7-containing neurons in the temporal cortices of patients with AD, without overall loss in neuron number (Banerjee et al., 2000). In addition to loss of neurons, there are reports of reduced expression of specific nAChR subtypes, particularly of alpha4beta2 and alpha7 subunits, in many brain areas in AD. PubMed:19293145

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Annotations
MeSH
Neurons

path(MESH:"Alzheimer Disease") increases p(HGNC:CHRNA7) View Subject | View Object

It is noteworthy that a different pattern of changes in nAChRs is seen in non-neuronal cells; expression levels of alpha7 have been reported to be elevated in astrocytes of brains from patients with AD and in cultured astrocytes (Teaktong et al., 2003; Xiu et al., 2005; Yu et al., 2005). Likewise, studies comparing alpha7 expression in human AD brain and Swedish-mutant mice found enhanced alpha7 expression in astrocytes but decreased expression in neurons compared with controls (Xiao et al., 2006). PubMed:19293145

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MeSH
Astrocytes

path(MESH:"Alzheimer Disease") decreases p(HGNC:CHRNA7) View Subject | View Object

Thus, predominantly alpha4 and alpha7 subunits, and to a lesser extent alpha3 subunits, are lost in AD, although there are tissue-specific differences to this pattern, such as the upregulation of nAChRs on astrocytes. PubMed:19293145

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path(MESH:"Alzheimer Disease") decreases p(HGNC:CHRNA7) View Subject | View Object

Thus, in brains from patients with AD and in neurons responding to exogenously applied Abeta, there is a reduction in expression of nAChR subunits, especially alpha4, alpha7, beta4, and possibly alpha3. Although AD may also involve changes in expression of other ligand-gated ion channels— for example, the expression of NMDA receptors (Bi and Sze, 2002; Jacob et al., 2007), alpha-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid receptors (Jacob et al., 2007), and beta3 GABA receptor subunits are all reduced (Mizukami et al., 1998)—there is abundant evidence of a loss of nAChR subunits in AD possibly caused by the actions of Abeta. PubMed:19293145

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MeSH
Brain

path(MESH:"Plaque, Amyloid") association p(HGNC:CHRNA7) View Subject | View Object

In addition, not only have alpha7 nAChRs been found colocalized with plaques (Wang et al., 2000b) but alpha7 and alpha4 subunits are also positively correlated with neurons that accumulate Abeta (Wevers et al., 1999). PubMed:19293145

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MeSH
Neurons

a(MESH:Ivermectin) increases act(p(HGNC:CHRNA7)) View Subject | View Object

The antihelminthic ivermectin was originally discovered to behave as a strong positive modulator of alpha􏰀7-nAChR PubMed:23038257

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a(CHEBI:"1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methyl-3-isoxazolyl)urea") regulates act(p(HGNC:CHRNA7)) View Subject | View Object

Another allosteric effector, 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596), dramatically modifies the response time course, ampliude of the current, and agonist sensitivity of the rat and human α7 nAChRs (70). PubMed:17009926

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a(CHEBI:"amyloid-beta") positiveCorrelation p(HGNC:CHRNA7) View Subject | View Object

This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161). PubMed:17009926

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Annotations
Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

a(CHEBI:acetylcholine) increases act(p(HGNC:CHRNA7)) View Subject | View Object

The α7 nAChR has a relatively low affinity for ACh activation, with an effective dose for half-activation at approximately 200 μM ACh. PubMed:17009926

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a(CHEBI:nicotine) increases act(p(HGNC:CHRNA7)) View Subject | View Object

Simultaneously, nicotine activates presynaptic α7∗ nAChRs, boosting glutamatergic synaptic transmission onto DA neurons (23, 88, 123, 134). PubMed:17009926

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MeSH
Presynaptic Terminals

a(HBP:"amyloid-beta aggregates") association p(HGNC:CHRNA7) View Subject | View Object

This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161). PubMed:17009926

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Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:5311278) decreases act(p(HGNC:CHRNA7)) View Subject | View Object

For example, local infusion of the α7 antagonist, methyllycaconitine (MLA), or the β2∗ antagonist, dihydro-β-erythroidine (DHβE), into the basolateral amygdala, the ventral hippocampus, or the dorsal hippocampus impairs the working memory of rats seeking food reward within a 16-arm radial maze (146–148). PubMed:17009926

Appears in Networks:
Annotations
MeSH
Amygdala
MeSH
Hippocampus

composite(a(CHEBI:"1,1-dimethyl-4-phenylpiperazinium iodide"), a(CHEBI:ivermectin)) increases act(p(HGNC:CHRNA7)) View Subject | View Object

Dimethylphenylpiperazidium (DMPP) normally is a partial agonist at this receptor subtype, but it becomes almost a full agonist following ivermectin exposure (68). PubMed:17009926

Appears in Networks:

composite(a(CHEBI:"5-hydroxyindole"), a(CHEBI:acetylcholine)) increases act(p(HGNC:CHRNA7)) View Subject | View Object

5-Hydroxy-indol (5-HI) allosterically increases the α7 ACh-induced responses without modifying the response time course or sensitivity to the agonist (69). PubMed:17009926

Appears in Networks:

p(HGNC:CHRNA7, pmod(Ph)) decreases act(p(HGNC:CHRNA7)) View Subject | View Object

Dephosphorylation of the α7 receptor by genistein causes a significant increase of ACh-evoked responses without modifying the response time course or ACh sensitivity (71, 72). PubMed:17009926

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) positiveCorrelation p(HGNC:CHRNA7) View Subject | View Object

This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161). PubMed:17009926

Appears in Networks:
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Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

a(CHEBI:nicotine) increases act(p(HGNC:CHRNA7)) View Subject | View Object

Those that contain β 2 ( β 2 * ) commonly have high affinity for nicotine, desensitize to low agonist con- centrations, have relatively slow kinetics, and do not bind α -bungarotoxin. PubMed:26472524

Appears in Networks:

p(HBP:"alpha-7-containing nAChR") increases act(p(HGNC:CHRNA7)) View Subject | View Object

For example, those that contain the α 7 subunit ( α 7 * ) as a homomeric or heteromeric receptor most commonly also have accompany- ing characteristics. They bind α -bungarotoxin, have relatively low affinity for nicotine and have relatively fast kinetics. PubMed:26472524

Appears in Networks:

a(MESH:"xestospongin C") decreases act(p(HGNC:CHRNA7)) View Subject | View Object

We confirmed the involvement of IP3Rs in choline-induced calcium transients at the GC of PC12 cells. Cells were preincubated with the IP3R blocker xestospongin C (1 μM) prior to imaging. As shown in Fig. 7, A–C, pretreatment with xestospongin C reduced the α7 nAChR calcium response peak by 46.82% in α7 cells (peak: 1308.43% ΔF/Fθ ± −238.13%; + xestospongin C = 695.80% ΔF/Fθ ± 101.46%). PubMed:26088141

Appears in Networks:
Annotations
MeSH
PC12 Cells

a(MESH:Barium) causesNoChange act(p(HGNC:CHRNA7)) View Subject | View Object

As shown in Fig. 5, A–C, barium replacement had little to no effect on the peak and total calcium transient observed in α7 (peak: 1474.83% ΔF/Fθ ± 162.00%; AUC: 693.5% ΔF/Fθ2 × s ± 154.15%) and α7345–348A expressing cells (peak: 794% ΔF/Fθ ± 81.36%; AUC: 543.5% ΔF/Fθ2 × s ± 89.59%). PubMed:26088141

Appears in Networks:

complex(p(FPLX:"G_beta"), p(FPLX:"G_gamma"), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7) increases p(HGNC:CHRNA7) View Subject | View Object

Western blot analysis confirms that transfection of α7 nAChRs augments total α7 subunit expression in PC12 cells, which express endogenous α7 nAChRs. Transfection with α7 (α7+) increased the immunoreactive α7 signal by over 60% from endogenous mock-transfected control cells, whereas transfection with the mutant α7345–348A increased the total α7 signal by 48% over the endogenous α7 from control cells (Fig. 3A). PubMed:26088141

Appears in Networks:
Annotations
MeSH
PC12 Cells

p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) increases p(HGNC:CHRNA7) View Subject | View Object

Western blot analysis confirms that transfection of α7 nAChRs augments total α7 subunit expression in PC12 cells, which express endogenous α7 nAChRs. Transfection with α7 (α7+) increased the immunoreactive α7 signal by over 60% from endogenous mock-transfected control cells, whereas transfection with the mutant α7345–348A increased the total α7 signal by 48% over the endogenous α7 from control cells (Fig. 3A). PubMed:26088141

Appears in Networks:
Annotations
MeSH
PC12 Cells

complex(p(FPLX:"G_protein"), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRNA7), p(HGNC:GNAI1)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRNA7), p(HGNC:GNAI2)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRNA7), p(HGNC:GNAQ)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRNA7), p(HGNC:GNAS)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRNA7), p(HGNCGENEFAMILY:"G protein subunits beta")) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

composite(a(CHEBI:choline), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

composite(p(HBP:"alpha-Bungarotoxin"), p(HGNC:CHRNA7), p(MESH:"Heterotrimeric GTP-Binding Proteins")) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) hasMember p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APP, frag("12_28")), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRNA7), p(HGNC:FLNA)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

complex(p(HGNC:APP), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

p(GFAM:"Cholinergic receptors nicotinic subunits") hasMember p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") negativeCorrelation p(HGNC:CHRNA7) View Subject | View Object

A decrease in the protein levels of the alpha3 and alpha4 nAChR subunits was recently measured in the temporal cortex and of the alpha3, alpha4, and alpha7 nAChR subtypes in the hippocampi of AD brains relative to age-matched control subjects (Guan et al 2000b) PubMed:11230871

Appears in Networks:
Annotations
MeSH
Hippocampus

a(CHEBI:"calcium(2+)") increases act(p(HGNC:CHRNA7)) View Subject | View Object

Most neuronal nAChRs, including alpha4beta2 and alpha7, are potentiated by Ca2+ at millimolar concentrations50. PubMed:19721446

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Text Location
Review

a(CHEBI:clozapine) association p(HGNC:CHRNA7) View Subject | View Object

However, the atypical antipsychotic drug clozapine normalizes auditory gating in DBA/2 mice — an effect which involves an alpha7 nAChR mechanism181. PubMed:19721446

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Text Location
Review

a(CHEBI:galanthamine) regulates p(HGNC:CHRNA7) View Subject | View Object

Two compounds that are currently in clinical use might have direct effects on the alpha7 nAChR. The anticholinesterase inhibitor galantamine has modulatory effects on alpha7 nAChR and was reportedly beneficial for patients with schizophrenia in a case study184 PubMed:19721446

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Text Location
Review

a(CHEBI:tropisetron) increases act(p(HGNC:CHRNA7)) View Subject | View Object

Similarly, topisetron, a 5HT3 antagonist marketed outside the united States as an anti-nausea drug, also has efficacy as an alpha7 nAChR agonist and increases the inhibition of P50 auditory gating in schizophrenia185. PubMed:19721446

Appears in Networks:
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MeSH
Schizophrenia
Text Location
Review

a(CHEBI:varenicline) increases act(p(HGNC:CHRNA7)) View Subject | View Object

varenicline (Chantix/Champix; Pfizer), the most recently approved drug for smoking cessation which is now on the market, is a partial agonist at alpha4beta2 nAChRs, and a full agonist at alpha7 nAChRs (ReF. 200). PubMed:19721446

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Text Location
Review

a(MESH:"3-(2,4-dimethoxybenzylidene)anabaseine") increases act(p(HGNC:CHRNA7)) View Subject | View Object

GTS-21, one of a series of compounds derived from anabaseine, an alkaloid found in marine worms, is a partial agonist of alpha7 nAChRs that improves memory-related behaviours in various paradigms and normalizes auditory gating186. it is the leading clinical candidate in the field of alpha7 nAChRs. PubMed:19721446

Appears in Networks:
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Text Location
Review

a(MESH:Hippocampus) association p(HGNC:CHRNA7) View Subject | View Object

First, there is a high level of expression of alpha7 nAChRs in the hippocampus, a region that is known to be involved in memory formation. Second, gene knockout and antisense studies have shown a role for alpha7 nAChRs in learning and memory144–146, and specifically in attention and working–episodic memory147,148. Third, pharmacological studies have shown that a range of structurally diverse alpha7 nAChR-selective agonists or positive allosteric modulators improve the cognitive deficits that are associated with Alzheimer’s disease. PubMed:19721446

Appears in Networks:
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Text Location
Review

bp(GO:cognition) positiveCorrelation p(HGNC:CHRNA7) View Subject | View Object

in the cerebral cortex, the massive reduction in nAChRs in Alzheimer’s disease128–130 involves predominantly the alpha4beta2 subtype, sparing the alpha7 subtype131. By contrast, in the hippocampus, a loss of alpha7 nAChRs seems to predominate and to correlate with the progressive loss of cognitive function132–136. PubMed:19721446

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease
Text Location
Review

bp(GO:learning) association p(HGNC:CHRNA7) View Subject | View Object

First, there is a high level of expression of alpha7 nAChRs in the hippocampus, a region that is known to be involved in memory formation. Second, gene knockout and antisense studies have shown a role for alpha7 nAChRs in learning and memory144–146, and specifically in attention and working–episodic memory147,148. Third, pharmacological studies have shown that a range of structurally diverse alpha7 nAChR-selective agonists or positive allosteric modulators improve the cognitive deficits that are associated with Alzheimer’s disease. PubMed:19721446

Appears in Networks:
Annotations
Text Location
Review

bp(GO:memory) association p(HGNC:CHRNA7) View Subject | View Object

First, there is a high level of expression of alpha7 nAChRs in the hippocampus, a region that is known to be involved in memory formation. Second, gene knockout and antisense studies have shown a role for alpha7 nAChRs in learning and memory144–146, and specifically in attention and working–episodic memory147,148. Third, pharmacological studies have shown that a range of structurally diverse alpha7 nAChR-selective agonists or positive allosteric modulators improve the cognitive deficits that are associated with Alzheimer’s disease. PubMed:19721446

Appears in Networks:
Annotations
Text Location
Review

bp(MESH:"Sensory Gating") association p(HGNC:CHRNA7) View Subject | View Object

in addition, a decrease in alpha7 nAChR density in the hippocampus of patients with schizophrenia has been reported177. Similarly, a low density of alpha7 nAChRs in inbred strains of mice is associated with poor gating178. Recently, the expression of a novel variant of alpha7 nAChR, CHRNA7-2 (cholinergic receptor, nicotinic, alpha7, variant 2), was found to be reduced below control levels in the prefrontal cortex of patients with schizophrenia179. PubMed:19721446

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Text Location
Review

bp(MESH:Neuroprotection) association p(HGNC:CHRNA7) View Subject | View Object

The alpha7 nAChR has previously been implicated in the in vitro neuroprotective effects of nicotine, using PC12 cells151. PubMed:19721446

Appears in Networks:
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Experimental Factor Ontology (EFO)
PC12
Text Location
Review

path(MESH:Schizophrenia) decreases p(HGNC:CHRNA7) View Subject | View Object

in addition, a decrease in alpha7 nAChR density in the hippocampus of patients with schizophrenia has been reported177. Similarly, a low density of alpha7 nAChRs in inbred strains of mice is associated with poor gating178. Recently, the expression of a novel variant of alpha7 nAChR, CHRNA7-2 (cholinergic receptor, nicotinic, alpha7, variant 2), was found to be reduced below control levels in the prefrontal cortex of patients with schizophrenia179. PubMed:19721446

Appears in Networks:
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MeSH
Hippocampus
Text Location
Review

act(a(MESH:"SNARE Proteins")) increases tloc(p(HGNC:CHRNA7), fromLoc(GO:"cell surface"), toLoc(GO:endosome)) View Subject | View Object

Furthermore, nicotinic stimulation rapidly induced SNARE-dependent vesicular endocytosis accompanied by receptor internalization [166]. However, the number of surface α7 AChRs was not modified since a SNARE-dependent pro- cess also recruited receptors to the cell surface from internal pools (Fig. 5). PubMed:22040696

Appears in Networks:

act(a(MESH:"SNARE Proteins")) causesNoChange surf(p(HGNC:CHRNA7)) View Subject | View Object

Furthermore, nicotinic stimulation rapidly induced SNARE-dependent vesicular endocytosis accompanied by receptor internalization [166]. However, the number of surface α7 AChRs was not modified since a SNARE-dependent pro- cess also recruited receptors to the cell surface from internal pools (Fig. 5). PubMed:22040696

Appears in Networks:

complex(a(CHEBI:"amyloid-beta"), p(HGNC:CHRNA7)) decreases act(p(HGNC:CHRNA7)) View Subject | View Object

Another important event that associates well with the Alzheimer disease pathology is the aggregation of the β-amyloid peptide [53]. This peptide interacts with α7 AChRs and has been reported to affect the nor- mal functioning of the latter, causing reduced neuronal survival [146,192–194]. PubMed:22040696

Appears in Networks:
Annotations
MeSH
Hippocampus

p(HGNC:RIC3) increases p(HGNC:CHRNA7) View Subject | View Object

It is noteworthy that RIC-3 has been shown to increase α7 AChR heterologous expression both in X. laevis oocytes and in HEK-293, CHO and SHE-P1 mammalian cell lines [66,71,77,107–112,119,125]. PubMed:22040696

Appears in Networks:

complex(p(HGNC:CHRNA7), p(HGNC:FYN)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRNA7), p(HGNC:JAK2)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRNA7), p(HGNC:RIC3)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

p(FPLX:Cyclophilin) increases p(HGNC:CHRNA7) View Subject | View Object

Additionally, the pro- lyl isomerase enzyme cyclophilin has been shown to be necessary for efficient folding of the α7 subunit in Xenopus oocytes [85–88]. PubMed:22040696

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p(HGNC:BDNF) association p(HGNC:CHRNA7) View Subject | View Object

BDNF can also influence the level of α7 AChRs subunits (Fig. 4) in the hippocampus and other brain regions [160,164,165]. PubMed:22040696

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Hippocampus

p(HGNC:BDNF) increases p(HGNC:CHRNA7) View Subject | View Object

Recent studies using dissociated rat hippocampal neurons in culture demonstrated that BDNF increases both surface and internal α7 AChRs pools. PubMed:22040696

Appears in Networks:

p(HGNC:BDNF) increases surf(p(HGNC:CHRNA7)) View Subject | View Object

Recent studies using dissociated rat hippocampal neurons in culture demonstrated that BDNF increases both surface and internal α7 AChRs pools. PubMed:22040696

Appears in Networks:

p(HGNC:CHRNA7, pmod(Ph, Tyr)) decreases act(p(HGNC:CHRNA7)) View Subject | View Object

Tyrosine phosphorylation of α7 AChR was found to negatively regulate receptor activity in neuroblastoma cells, hippo- campal CA1 interneurons, and supraoptic magnocellular neurons, whereas de-phosphorylation of α7 AChR was found to potentiate ACh-evoked currents in these cells. PubMed:22040696

Appears in Networks:

p(HGNC:CHRNA7, var("p.Leu335Ala")) decreases surf(p(HGNC:CHRNA7)) View Subject | View Object

A recent study showed that mutation of amino acids from this region (leucines 335, 336 or 343) to alanine reduced cell-surface expression of α7 AChRs [173]. PubMed:22040696

Appears in Networks:

p(HGNC:CHRNA7, var("p.Leu336Ala")) decreases surf(p(HGNC:CHRNA7)) View Subject | View Object

A recent study showed that mutation of amino acids from this region (leucines 335, 336 or 343) to alanine reduced cell-surface expression of α7 AChRs [173]. PubMed:22040696

Appears in Networks:

p(HGNC:CHRNA7, var("p.Leu343Ala")) decreases surf(p(HGNC:CHRNA7)) View Subject | View Object

A recent study showed that mutation of amino acids from this region (leucines 335, 336 or 343) to alanine reduced cell-surface expression of α7 AChRs [173]. PubMed:22040696

Appears in Networks:

path(MESH:"Alzheimer Disease") negativeCorrelation p(HGNC:CHRNA7) View Subject | View Object

Reduction of α7 AChRs in the CNS is linked with Alzheimer dis- ease, which has been shown to lead to neuronal loss [53,188–190]. PubMed:22040696

Appears in Networks:
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MeSH
Central Nervous System

path(MESH:"Neurodegenerative Diseases") association p(HGNC:CHRNA7) View Subject | View Object

AChRs have been linked to many neurodegenerative disorders [13,47–60]. PubMed:22040696

Appears in Networks:

path(MESH:Schizophrenia) negativeCorrelation p(HGNC:CHRNA7) View Subject | View Object

Decreased expression of α7 AChR has also been associated with schizophrenia [51,195–197]. PubMed:22040696

Appears in Networks:
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MeSH
Hippocampus

a(MESH:Nicotine) increases act(p(HGNC:CHRNA7)) View Subject | View Object

Chronic nicotine treatment also activates the α7 receptors expressed on glutamatergic terminals, increases the release of glutamate (which facilitates the burst firing of VTA DA neurons), increases NMDA receptor activity, and LTP [79], but simultaneosusly induces the desensitisation of the α4β2 receptors on GABAergic terminals. Overall, these effects decrease the inhibition onto DA neurons, and increase DA release in the NAc [82]. PubMed:28901280

Appears in Networks:
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MeSH
GABAergic Neurons

a(MESH:Nicotine) decreases act(p(HGNC:CHRNA7)) View Subject | View Object

These alterations are very similar to those observed in cul- tured human airway cells or in ex vivo human lung explants treated with the selective α7 antagonist αBgtx, or epithelial cell cultures chronically exposed to nicotine in which nico- tine-induced desensitisation of α7 receptors mimics the ab- sence of α7 nAChR PubMed:28901280

Appears in Networks:
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MeSH
GABAergic Neurons

complex(p(HGNC:CHRNA5), p(HGNC:CHRNA7), p(HGNC:CHRNB2), p(HGNC:CHRNB3), p(HGNC:CHRNB4)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

p(HGNC:CHRFAM7A, loc(MESH:Oocytes)) decreases act(p(HGNC:CHRNA7, loc(MESH:Oocytes))) View Subject | View Object

Functional studies have shown that α7dup, expressed in oo- cytes, acts as a dominant negative regulator of α7 nAChR activity by means of a mechanism involving a reduction in the number of functional α7 nAChRs incorporated into the oocyte surface PubMed:28901280

Appears in Networks:

p(HGNC:LYNX1) decreases act(p(HGNC:CHRNA7)) View Subject | View Object

These proteins include Lynx1, a glycophosphati- dylinositol- anchored membrane protein that can form a sta- ble complex, negatively regulates the responses of α4β2 and α7 nAChRs in heterologous systems and enhances the rate and extent of desensitisation of α4β2 nAChRs, thus acting as a molecular brake on nAChR function PubMed:28901280

Appears in Networks:
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MeSH
GABAergic Neurons

path(MESH:Neoplasms) association p(HGNC:CHRNA7) View Subject | View Object

In addition, various studies have shown the expression of α7 nAChR (as mRNA and protein), in many different cancer cells obtained from human tumours. PubMed:28901280

Appears in Networks:
Annotations
MeSH
GABAergic Neurons

a(CHEBI:Anatabine) increases act(p(HGNC:CHRNA7)) View Subject | View Object

Anatabine has a chemical structure closely related to nicotine and is a full agonist of α7 and α4β2 nicotinic acetylcholine receptors (nAChR) but is a more potent α7 nAChR agonist than nicotine [15,16]. PubMed:26010758

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composite(p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")), p(HGNC:CHRNA7)) hasComponent p(HGNC:CHRNA7) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:CHRNA7) View Subject | View Object

AD brains show an upregulation of CHRNA7 (acr-14 homolog in humans) (84), where it may mediate the Ab-induced tau pathology (85). PubMed:29191965

Appears in Networks:
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MeSH
Brain

path(MESH:Tauopathies) association p(HGNC:CHRNA7) View Subject | View Object

Some of these enhancer genes are specific only to the tau-induced disease phenotype and include genes encoding proteins like WNT2 (111), TTBK2 (112), GSK-3b (113), TAOK1 (114, 115), CTSE (116) and CHRNA7 (117), have been implicated in tau-mediated pathology. PubMed:29191965

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Out-Edges 111

p(HGNC:CHRNA7) hasVariant p(HGNC:CHRNA7, pmod(Ph, Tyr)) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7) hasVariant p(HGNC:CHRNA7, var("p.Leu335Ala")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7) hasVariant p(HGNC:CHRNA7, var("p.Leu336Ala")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7) hasVariant p(HGNC:CHRNA7, var("p.Leu343Ala")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7) hasVariant p(HGNC:CHRNA7, frag("23_46")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7) association a(MESH:Neurons) View Subject | View Object

For example, while the alpha7 nAChR is primarily a homomeric receptor in neurons (127), combinations of alpha7 nAChR subunits with alpha5, beta2, or beta3 nAChR subunits have been reported to form functional heteromeric receptors in some systems (240, 360, 515). PubMed:19126755

Appears in Networks:
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Text Location
Review

p(HGNC:CHRNA7) association complex(p(HGNC:CHRNA5), p(HGNC:CHRNA7)) View Subject | View Object

For example, while the alpha7 nAChR is primarily a homomeric receptor in neurons (127), combinations of alpha7 nAChR subunits with alpha5, beta2, or beta3 nAChR subunits have been reported to form functional heteromeric receptors in some systems (240, 360, 515). PubMed:19126755

Appears in Networks:
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Text Location
Review

p(HGNC:CHRNA7) association complex(p(HGNC:CHRNA7), p(HGNC:CHRNB2)) View Subject | View Object

For example, while the alpha7 nAChR is primarily a homomeric receptor in neurons (127), combinations of alpha7 nAChR subunits with alpha5, beta2, or beta3 nAChR subunits have been reported to form functional heteromeric receptors in some systems (240, 360, 515). PubMed:19126755

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:CHRNA7) association complex(p(HGNC:CHRNA7), p(HGNC:CHRNB3)) View Subject | View Object

For example, while the alpha7 nAChR is primarily a homomeric receptor in neurons (127), combinations of alpha7 nAChR subunits with alpha5, beta2, or beta3 nAChR subunits have been reported to form functional heteromeric receptors in some systems (240, 360, 515). PubMed:19126755

Appears in Networks:
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Text Location
Review

act(p(HGNC:CHRNA7)) increases bp(GO:"action potential initiation") View Subject | View Object

It is noteworthy that, via such mechanisms, alpha7 nAChR activation could trigger rebound burst firing in SLM interneurons even in the absence of excitation (256). Burst firing in SLM interneurons suppresses spikes in pyramidal neurons evoked by stimulation of Schaffer collaterals (134), and, thereby allows selective activation of the pyramidal cells via the perforant pathway. PubMed:19126755

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Annotations
Uberon
hippocampus stratum lacunosum moleculare
Text Location
Review

act(p(HGNC:CHRNA7, loc(GO:"axon terminus"))) regulates bp(GO:"synaptic transmission, glycinergic") View Subject | View Object

In CA1 and CA3 pyramidal neurons of the developed hippocampus, alpha7 nAChRs are expressed primarily on axon terminals whereby their activation modulates the efficacy of glutamate synaptic transmission. PubMed:19126755

Appears in Networks:
Annotations
MeSH
CA1 Region, Hippocampal
MeSH
CA3 Region, Hippocampal
MeSH
Pyramidal Cells
Text Location
Review

act(p(HGNC:CHRNA7)) increases a(CHEBI:"calcium(2+)", loc(GO:intracellular)) View Subject | View Object

For example, during a low degree of activation of alpha7 and alpha3beta4 nAChRs, Ca2+ can enter the cells through nAChRs or NMDA receptors and favor activation (i.e., phosphorylation) of the transcription factor CREB, which in turn modifies gene expression (82). PubMed:19126755

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Text Location
Review

act(p(HGNC:CHRNA7)) increases a(CHEBI:"calcium(2+)", loc(GO:intracellular)) View Subject | View Object

Long before the identification of the high Ca2+ permeability of alpha7 nAChR channels, different studies reported significant Ca2+ influx through nAChRs in muscle, parasympathetic neurons, pheochromocytoma cells, and human neuroblastoma cells (115, 321, 347, 407, 411, 459, 468). PubMed:19126755

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Text Location
Review

act(p(HGNC:CHRNA7)) increases bp(GO:"neuronal action potential") View Subject | View Object

Activation of somatodendritic alpha7 nAChRs increases the action potential-dependent release of dopamine, while activation of presynaptic alpha6 and/or alpha4 nAChRs increases action potential-independent dopamine release. PubMed:19126755

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Text Location
Review

act(p(HGNC:CHRNA7, loc(GO:"glutamatergic synapse"))) regulates bp(GO:"synaptic transmission, dopaminergic") View Subject | View Object

Other levels of regulation of dopaminergic transmission arise from alpha7 nAChRs located on cortical glutamatergic terminals; activation of these receptors increases glutamate release onto dopaminergic neurons in the VTA and, consequently, increases the their firing (344). PubMed:19126755

Appears in Networks:
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Text Location
Review

act(p(HGNC:CHRNA7, loc(GO:"glutamatergic synapse"))) increases a(CHEBI:"glutamate(2-)", loc(MESH:"Dopaminergic Neurons")) View Subject | View Object

Other levels of regulation of dopaminergic transmission arise from alpha7 nAChRs located on cortical glutamatergic terminals; activation of these receptors increases glutamate release onto dopaminergic neurons in the VTA and, consequently, increases the their firing (344). PubMed:19126755

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:CHRNA7, loc(MESH:"Mossy Fibers, Hippocampal")) regulates a(CHEBI:"glutamate(2-)", loc(MESH:"Pyramidal Cells")) View Subject | View Object

Activation of alpha7 nAChRs in somatodendritic and preterminal/ terminal areas of interneurons in various strata of the CA1 region and in the dentate gyrus facilitates spontaneous quantal release of GABA (14, 25). Glutamate release from mossy fibers onto CA3 pyramidal neurons is also modulated by alpha7 nAChRs present in the mossy fiber terminals (190). PubMed:19126755

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MeSH
CA1 Region, Hippocampal
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Review

p(HGNC:CHRNA7) positiveCorrelation bp(GO:cognition) View Subject | View Object

In particular, the association of the alpha7 nAChR gene with a sensory gating deficit that is similar to attention deficits in patients with schizophrenia (157), and the degree of alpha4beta2 nAChR loss and altered alpha7 expresson correlate well with the magnitude of progressive cognitive decline in mild-to-moderate AD patients (46). PubMed:19126755

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act(p(HGNC:CHRNA7)) association bp(GO:cognition) View Subject | View Object

Chronic alpha7 nAChR inhibition in the hippocampus by elevated levels of KYNA can contribute to auditory gating deficits, which appear to be associated with the development of schizophrenia (156). It is also feasible that KYNAinduced inhibition of alpha7 nAChRs contributes to the cognitive impairment observed in patients with AD and schizophrenia (273). PubMed:19126755

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MeSH
Hippocampus
Text Location
Review

p(HGNC:CHRNA7) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

In particular, the association of the alpha7 nAChR gene with a sensory gating deficit that is similar to attention deficits in patients with schizophrenia (157), and the degree of alpha4beta2 nAChR loss and altered alpha7 expresson correlate well with the magnitude of progressive cognitive decline in mild-to-moderate AD patients (46). PubMed:19126755

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Review

act(p(HGNC:CHRNA7)) increases sec(a(CHEBI:"gamma-aminobutyric acid")) View Subject | View Object

Activation of alpha7 nAChRs in somatodendritic and preterminal/ terminal areas of interneurons in various strata of the CA1 region and in the dentate gyrus facilitates spontaneous quantal release of GABA (14, 25). Glutamate release from mossy fibers onto CA3 pyramidal neurons is also modulated by alpha7 nAChRs present in the mossy fiber terminals (190). PubMed:19126755

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MeSH
CA1 Region, Hippocampal
Text Location
Review

act(p(HGNC:CHRNA7)) regulates a(CHEBI:dopamine, loc(GO:"extracellular region")) View Subject | View Object

Activation of alpha7 nAChRs is known to contribute to the regulation of extracellular dopamine levels in the rat striatum (81). Application via microdialysis of KYNA or alpha-BGT to the rat striatum significantly reduces the extracellular levels of dopamine, and the magnitude of the effect of either antagonist alone is comparable to that of both antagonists together (285). PubMed:19126755

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MeSH
Corpus Striatum
Text Location
Review

act(p(HGNC:CHRNA7)) increases a(CHEBI:dopamine, loc(GO:"extracellular region")) View Subject | View Object

As illustrated in Figure 8, KYNA-induced reduction of extracellular dopamine levels can be explained by the inhibition of tonically active alpha7 nAChRs in the dopaminergic neurons within the VTA and/or in cortical glutamatergic terminals that synapse onto striatal neurons. VTA dopaminergic neurons represent the major dopaminergic input to the nucleus accumbens. PubMed:19126755

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MeSH
Dopaminergic Neurons
Text Location
Review

act(p(HGNC:CHRNA7)) association path(MESH:"Sensory Gating") View Subject | View Object

Chronic alpha7 nAChR inhibition in the hippocampus by elevated levels of KYNA can contribute to auditory gating deficits, which appear to be associated with the development of schizophrenia (156). It is also feasible that KYNAinduced inhibition of alpha7 nAChRs contributes to the cognitive impairment observed in patients with AD and schizophrenia (273). PubMed:19126755

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MeSH
Hippocampus
Text Location
Review

act(p(HGNC:CHRNA7)) increases a(CHEBI:"amyloid-beta", loc(GO:intracellular)) View Subject | View Object

It is noteworthy that the alpha7 nAChR activity increases intracellular accumulation of Abeta in neurons (336), and Abeta peptides, in addition to modulating nAChR activity, downregulate the expression of nAChRs (197). PubMed:19126755

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MeSH
Neurons
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Review

act(p(HGNC:CHRNA7)) increases a(CHEBI:anandamide) View Subject | View Object

There is evidence that anandamide is produced by postsynaptic neurons in response to elevated intracellular Ca2+ levels. For instance, concomitant activation of alpha7 nAChRs and NMDA receptors triggers the production of anandamine in postsynaptic neurons (448). Anandamine, then, functions as a retrograde messenger and regulates synaptic transmission by interacting with specific receptors in the presynaptic neurons/terminals (498). PubMed:19126755

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Neurons
Text Location
Review

p(HGNC:CHRNA7) regulates bp(GO:"cell cycle") View Subject | View Object

Furthermore, pharmacological dissection of nicotine’s influence on cell cycle progression, apoptosis, and differentiation (43) indicate that alpha7 nAChRs expressed in keratynocytes are important. Other receptors are clearly involved in this process, since atropine, a muscarinic and sometimes nAChR inhibitor (531, 532), reduces cell adhesion through decreasing desmoligein expression. PubMed:19126755

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MeSH
Keratinocytes
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Review

act(p(HGNC:CHRNA7)) association a(CHEBI:nicotine) View Subject | View Object

A principle component of genetic analysis of the contribution of alpha7 and alpha4beta2 nAChRs to the effects of nicotine was reported 15 years ago. The number of alpha-BGT binding sites (presumably alpha7 nAChRs) was shown to be highly correlated with sensitivity to nicotinic-induced seizures (105, 301, 303). PubMed:19126755

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MeSH
Seizures
Text Location
Review

p(HGNC:CHRNA7) regulates a(CHEBI:nicotine) View Subject | View Object

Several possibilities exist for the identity of the nAChR important to tolerance development. The strong positive correlation between alpha-BGT site number and sensitivity to nicotine-induced seizures among multiple mouse strains led to the suggestion that alpha7 nAChRs are critical to limit oral nicotine self-administration in mice (105, 301). PubMed:19126755

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Review

p(HGNC:CHRNA7) regulates path(MESH:"Substance Withdrawal Syndrome") View Subject | View Object

While development of tolerance does not seem to be regulated by alpha7 nAChRs, a recent study of alpha7 nAChR-null mice indicates that these receptors control the severity of the nicotine withdrawal syndrome (402). PubMed:19126755

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Review

p(HGNC:CHRNA7) hasVariant p(HGNC:CHRNA7, var("?")) View Subject | View Object

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p(HGNC:CHRNA7) hasVariant p(HGNC:CHRNA7, var("p.L250T")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7) hasVariant p(HGNC:CHRNA7, var("p.Trp55Ala")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7) hasVariant p(HGNC:CHRNA7, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7) association path(MESH:"Alzheimer Disease") View Subject | View Object

Genetic association studies investigating single nucleotide polymorphisms point to roles for cholinergic signaling components such as the synthetic enzyme ChAT, the inactivating enzyme AChE, and alpha4beta2 nAChRs in AD (Cook et al., 2004, 2005; Vasto et al., 2006). The most vulnerable neurons in AD seem to be those expressing high levels of nAChRs, particularly those containing the alpha7 subunit (D’Andrea and Nagele, 2006), and the numbers of nAChRs as well as some of their associated proteins change in AD (Martin-Ruiz et al., 1999; Gotti et al., 2006; Sabbagh et al., 2006). PubMed:19293145

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p(HGNC:CHRNA7) association path(MESH:"Plaque, Amyloid") View Subject | View Object

In addition, not only have alpha7 nAChRs been found colocalized with plaques (Wang et al., 2000b) but alpha7 and alpha4 subunits are also positively correlated with neurons that accumulate Abeta (Wevers et al., 1999). PubMed:19293145

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MeSH
Neurons

p(HGNC:CHRNA7) positiveCorrelation a(CHEBI:"amyloid-beta") View Subject | View Object

In addition, not only have alpha7 nAChRs been found colocalized with plaques (Wang et al., 2000b) but alpha7 and alpha4 subunits are also positively correlated with neurons that accumulate Abeta (Wevers et al., 1999). PubMed:19293145

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MeSH
Neurons

p(HGNC:CHRNA7) decreases act(a(CHEBI:"amyloid-beta")) View Subject | View Object

In SHSY5Y cells, RNA interference (RNAi) knockdown of alpha7 enhanced Abeta toxicity (Qi et al., 2007), and alpha7 antagonists, but not alpha4beta2 antagonists, block galantamine protection of cultured rat neurons (Kihara et al., 2004). Donepezil protects cultured rat cortical neurons against Abeta toxicity through both alpha7 and non-alpha7 nAChRs (Takada et al., 2003). It is therefore likely that alpha7 nAChRs are the primary mediators of nicotine neuroprotection, but in some cells, non-alpha7 subtypes are also likely to contribute. PubMed:19293145

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p(HGNC:CHRNA7) increases a(CHEBI:"amyloid-beta") View Subject | View Object

An indication that nAChRs may play a role in Abeta internalization comes from a close inspection of cholinergic neurons in brains from patients with AD, which revealed that neurons with high expression levels of alpha7 also contained large amounts of intracellular Abeta (Nagele et al., 2002). Addition of Abeta to the culture medium of neuroblastoma cells overexpressing alpha7 results in more Abeta internalization than in control cells with lower levels of alpha7 expression (Nagele et al., 2002). PubMed:19293145

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MeSH
Brain
MeSH
Neurons
MeSH
Alzheimer Disease

p(HGNC:CHRNA7) association a(CHEBI:"amyloid-beta") View Subject | View Object

In contrast, Small et al. (2007) found no displacement of alpha-BTX from SH-SY5Y cells (a cell line very closely related to that used by Wang et al.) by either amyloid or methyllycaconitine. Wang et al. (2000b) also showed similar staining of human AD cortical neurons by alpha7 and Abeta antibodies in double immunofluorescence, suggesting that in human cortical neurons, alpha7 and Abeta are closely associated, although such an approach does not prove direct binding. However another study (Small et al., 2007) showed no displacement of labeled alpha-bungarotoxin from cell lines expressing rat alpha7 nAChRs. PubMed:19293145

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Experimental Factor Ontology (EFO)
SH-SY5Y

p(HGNC:CHRNA7) increases act(a(CHEBI:galanthamine)) View Subject | View Object

In SHSY5Y cells, RNA interference (RNAi) knockdown of alpha7 enhanced Abeta toxicity (Qi et al., 2007), and alpha7 antagonists, but not alpha4beta2 antagonists, block galantamine protection of cultured rat neurons (Kihara et al., 2004). Donepezil protects cultured rat cortical neurons against Abeta toxicity through both alpha7 and non-alpha7 nAChRs (Takada et al., 2003). It is therefore likely that alpha7 nAChRs are the primary mediators of nicotine neuroprotection, but in some cells, non-alpha7 subtypes are also likely to contribute. PubMed:19293145

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p(HGNC:CHRNA7) regulates act(a(CHEBI:nicotine)) View Subject | View Object

In SHSY5Y cells, RNA interference (RNAi) knockdown of alpha7 enhanced Abeta toxicity (Qi et al., 2007), and alpha7 antagonists, but not alpha4beta2 antagonists, block galantamine protection of cultured rat neurons (Kihara et al., 2004). Donepezil protects cultured rat cortical neurons against Abeta toxicity through both alpha7 and non-alpha7 nAChRs (Takada et al., 2003). It is therefore likely that alpha7 nAChRs are the primary mediators of nicotine neuroprotection, but in some cells, non-alpha7 subtypes are also likely to contribute. PubMed:19293145

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p(HGNC:CHRNA7) increases a(CHEBI:nicotine) View Subject | View Object

Nicotine stimulates the secretion of betaAPP, which is trophic and neuroprotective against Abeta, from PC12 cells through an alpha7 and calcium-dependent pathway (Kim et al., 1997) as well as increasing the secretion of soluble APP and lowering the Abeta-containing sAPP-gamma in rats (Lahiri et al., 2002), again through nAChR-dependent mechanisms. Galantamine, a nAChR potentiator and AChE inhibitor, also increases the secretion of sAPP from human SH-SY5Y neuroblastoma cells (Lenzken et al., 2007) through the activation of nAChRs. It therefore seems that activation of nAChRs shifts the balance of APP processing away from beta-amyloidogenic to soluble APP production. PubMed:19293145

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Experimental Factor Ontology (EFO)
PC12

act(p(HGNC:CHRNA7)) decreases act(a(CHEBI:ethanol)) View Subject | View Object

Nicotinic neuroprotection against non-Abeta toxicity is also mediated largely through alpha7 nAChRs. alpha7 nAChRs protect PC12 cells against ethanol toxicity (Li et al., 1999a) and from cell death associated with serum depletion (Ren et al., 2005); they protect cultured neurons against glutamate-induced excitotoxicity (Kaneko et al., 1997) and hippocampal slices against oxygen and glucose deprivation (Egea et al., 2007) through the activation of alpha7 nAChRs (Rosa et al., 2006). PubMed:19293145

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Experimental Factor Ontology (EFO)
PC12

act(p(HGNC:CHRNA7)) decreases bp(GO:"cell death") View Subject | View Object

Nicotinic neuroprotection against non-Abeta toxicity is also mediated largely through alpha7 nAChRs. alpha7 nAChRs protect PC12 cells against ethanol toxicity (Li et al., 1999a) and from cell death associated with serum depletion (Ren et al., 2005); they protect cultured neurons against glutamate-induced excitotoxicity (Kaneko et al., 1997) and hippocampal slices against oxygen and glucose deprivation (Egea et al., 2007) through the activation of alpha7 nAChRs (Rosa et al., 2006). PubMed:19293145

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Experimental Factor Ontology (EFO)
PC12

act(p(HGNC:CHRNA7)) decreases act(a(CHEBI:"glutamate(2-)")) View Subject | View Object

Nicotinic neuroprotection against non-Abeta toxicity is also mediated largely through alpha7 nAChRs. alpha7 nAChRs protect PC12 cells against ethanol toxicity (Li et al., 1999a) and from cell death associated with serum depletion (Ren et al., 2005); they protect cultured neurons against glutamate-induced excitotoxicity (Kaneko et al., 1997) and hippocampal slices against oxygen and glucose deprivation (Egea et al., 2007) through the activation of alpha7 nAChRs (Rosa et al., 2006). PubMed:19293145

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MeSH
Neurons

act(p(HGNC:CHRNA7)) increases a(CHEBI:glucose) View Subject | View Object

Nicotinic neuroprotection against non-Abeta toxicity is also mediated largely through alpha7 nAChRs. alpha7 nAChRs protect PC12 cells against ethanol toxicity (Li et al., 1999a) and from cell death associated with serum depletion (Ren et al., 2005); they protect cultured neurons against glutamate-induced excitotoxicity (Kaneko et al., 1997) and hippocampal slices against oxygen and glucose deprivation (Egea et al., 2007) through the activation of alpha7 nAChRs (Rosa et al., 2006). PubMed:19293145

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MeSH
Hippocampus

act(p(HGNC:CHRNA7)) increases a(MESH:Oxygen) View Subject | View Object

Nicotinic neuroprotection against non-Abeta toxicity is also mediated largely through alpha7 nAChRs. alpha7 nAChRs protect PC12 cells against ethanol toxicity (Li et al., 1999a) and from cell death associated with serum depletion (Ren et al., 2005); they protect cultured neurons against glutamate-induced excitotoxicity (Kaneko et al., 1997) and hippocampal slices against oxygen and glucose deprivation (Egea et al., 2007) through the activation of alpha7 nAChRs (Rosa et al., 2006). PubMed:19293145

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MeSH
Hippocampus

act(p(HGNC:CHRNA7)) decreases act(a(CHEBI:"L-glutamate(2-)")) View Subject | View Object

For example, alpha4-specific agonists protect porcine small retinal ganglion cells against L-glutamate toxicity (Thompson et al., 2006), whereas alpha7 nAChRs protect large retinal ganglion cells (Wehrwein et al., 2004) against L-glutamate toxicity. PubMed:19293145

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MeSH
Retinal Ganglion Cells

act(p(HGNC:CHRNA7)) causesNoChange act(a(CHEBI:"N-methyl-4-phenylpyridinium")) View Subject | View Object

For example, non-alpha7 nAChRs protect cultured nigral dopaminergic neurons from toxicity induced by 1-methyl-4-phenylpyridinium, a neurotoxin that selectively damages nigrostriatal dopaminergic neurons (Jeyarasasingam et al., 2002), and this effect is not mediated by alpha7 receptors. PubMed:19293145

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MeSH
Dopaminergic Neurons

act(p(HGNC:CHRNA7)) decreases act(p(HGNC:FAS)) View Subject | View Object

Hepatic vagus nerve activity has recently been shown to protect hepatocytes from Fas-induced apoptosis via activation of alpha7 nAChRs (Hiramoto et al., 2008). Thus, nicotine seems to exert a general pro-survival action not only on neurons but also on non-neuronal cells, suggesting that the protection offered by nicotine against Abeta toxicity may therefore simply be the result of a general pro-survival response. PubMed:19293145

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MeSH
Liver

act(p(HGNC:CHRNA7)) increases act(p(HGNC:JAK2)) View Subject | View Object

Nicotine induced phosphorylation of STAT-3 (signal transducer and activator of transcription 3) in peritoneal macrophages is mediated by an alpha7-dependent activation of JAK-2, as part of the anti-inflammatory action of vagal nerve stimulation (de Jonge et al., 2005). PubMed:19293145

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Cell Ontology (CL)
peritoneal macrophage

p(HGNC:CHRNA7) increases bp(GO:"MAPK cascade") View Subject | View Object

Application of nicotine to rat microglia results in the up-regulated expression of cyclooxygenase-2 and prostaglandin E2 (De Simone et al., 2005). Signaling pathways downstream to the MAPK pathway are similarly well placed to effect changes in gene expression. For example, alpha7-dependent activation of the MAPK pathway is known to activate c-Myc (Liu et al., 2007), a protooncogene whose transcription product sensitizes cells to pro-apoptotic stimuli. PubMed:19293145

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Cell Ontology (CL)
microglial cell

p(HGNC:CHRNA7) increases bp(GO:"MAPK cascade") View Subject | View Object

Nicotine also activates ERK in non-neuronal cells such as pancreatic acinar cells (Chowdhury et al., 2007) and vascular smooth muscle cells (Kanda and Watanabe, 2007), although it is not known in those cases which nAChR subtypes are involved. In the cortex and hippocampus of mice, nicotine’s inhibition of MAPK (shown by RNAi reduction of alpha7 expression to be alpha7-dependent) prevents activation of nuclear factor- kappaB and c-Myc, also thereby reducing the activity of inducible nitric-oxide synthetase and NO production and decreasing Abeta production (Liu et al., 2007). PubMed:19293145

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Cell Ontology (CL)
pancreatic acinar cell
Cell Ontology (CL)
vascular associated smooth muscle cell

act(p(HGNC:CHRNA7)) increases bp(GO:"calcium ion transport") View Subject | View Object

Calcium signaling pathways are involved both in the toxic action of Abeta and in the protection against that toxicity offered by nicotinic ligands. Given that alpha7 homomeric nAChRs are much more permeable to calcium ions than are most other nAChRs (Bertrand et al., 1993), it is to be expected that nicotinic neuroprotection mediated by nAChRs, notably alpha7, would depend upon the activation of calcium signaling pathways. ABT-418 is a nicotinic agonist that protects primary rat cortical neurons from glutamate toxicity through its activation of alpha7 nAChRs, and this is blocked when calcium is removed from the extracellular medium (Donnelly-Roberts et al., 1996). PubMed:19293145

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act(p(HGNC:CHRNA7)) association bp(GO:"calcium-mediated signaling") View Subject | View Object

Calcium signaling pathways are involved both in the toxic action of Abeta and in the protection against that toxicity offered by nicotinic ligands. Given that alpha7 homomeric nAChRs are much more permeable to calcium ions than are most other nAChRs (Bertrand et al., 1993), it is to be expected that nicotinic neuroprotection mediated by nAChRs, notably alpha7, would depend upon the activation of calcium signaling pathways. ABT-418 is a nicotinic agonist that protects primary rat cortical neurons from glutamate toxicity through its activation of alpha7 nAChRs, and this is blocked when calcium is removed from the extracellular medium (Donnelly-Roberts et al., 1996). PubMed:19293145

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p(HGNC:CHRNA7) increases act(p(HGNCGENEFAMILY:"Ryanodine receptors")) View Subject | View Object

It has been shown that the alpha7 receptors, but not the alpha3beta2 receptors, specifically trigger calcium release from intracellular stores by activating ryanodine receptors. Such a specific functional coupling of alpha7 receptors and ryanodine-sensitive stores may provide another site of therapeutic intervention. However, the sustained calcium rise seen in these cells upon prolonged nicotine administration, which is more likely to be of relevance to neuroprotection than short-term responses, is more dependent upon the activation of inositol 1,4,5-triphosphate receptors (Dajas-Bailador et al., 2002a), which are also a target for phosphorylation by FYN (Cui et al., 2004). PubMed:19293145

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act(p(HGNC:CHRNA7)) increases a(CHEBI:"calcium(2+)") View Subject | View Object

Abeta1–42 activates heterologously expressed nAChRs (Dineley et al., 2002), and Abeta25–35 has been shown to activate non-alpha7 nAChRs in rat basal forebrain neurons (Fu and Jhamandas, 2003) and to evoke a alpha7- mediated calcium increases in presynaptic terminals isolated from rat hippocampus and neocortex (Dougherty et al., 2003). PubMed:19293145

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p(HGNC:CHRNA7) hasVariant p(HGNC:CHRNA7, var("p.Leu254Thr")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7) hasVariant p(HGNC:CHRNA7, var("p.Leu255Thr")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7) increases bp(GO:"neurotransmitter secretion") View Subject | View Object

In some cases, the highly calcium-permeable α7-containing (α7∗) nAChRs mediate the increased release of neurotransmitter, but in other cases different nAChR subtypes are involved. PubMed:17009926

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p(HGNC:CHRNA7) increases act(complex(GO:"voltage-gated calcium channel complex")) View Subject | View Object

Preterminal nAChRs located before the presynaptic terminal bouton indirectly affect neurotransmitter release by activating voltage-gated channels and, potentially, initiating action potentials (78, 91, 93). PubMed:17009926

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act(p(HGNC:CHRNA7)) increases bp(GO:"synaptic transmission, glutamatergic") View Subject | View Object

Simultaneously, nicotine activates presynaptic α7∗ nAChRs, boosting glutamatergic synaptic transmission onto DA neurons (23, 88, 123, 134). PubMed:17009926

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Cell Ontology (CL)
dopaminergic neuron

act(p(HGNC:CHRNA7)) increases sec(a(CHEBI:"glutamate(2-)")) View Subject | View Object

Postsynaptic β2∗ nAChRs initially depolarize DA neurons, causing them to fire action potentials while presynaptic α7∗ nAChRs boost glutamate release. PubMed:17009926

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Cell Ontology (CL)
dopaminergic neuron
MeSH
Presynaptic Terminals

p(HGNC:CHRNA7) association a(HBP:"amyloid-beta aggregates") View Subject | View Object

This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161). PubMed:17009926

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:CHRNA7) positiveCorrelation a(CHEBI:"amyloid-beta") View Subject | View Object

This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161). PubMed:17009926

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:CHRNA7) positiveCorrelation p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161). PubMed:17009926

Appears in Networks:
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Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:CHRNA7) increases a(MESH:"Receptors, Nicotinic") View Subject | View Object

On the other hand, neuronal nicotinic receptors are formed by the combination of only two types of subunits (α2-10 and β2-4) PubMed:26813123

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MeSH
Neurons

p(HGNC:CHRNA7) hasVariant p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7) increases bp(HBP:"nAChR assembly") View Subject | View Object

The findings confirm that the mutation in α7345–348A does not interfere with the trafficking or expression of the nAChR. PubMed:26088141

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p(HGNC:CHRNA7) increases p(HGNC:CHRNA7) View Subject | View Object

Western blot analysis confirms that transfection of α7 nAChRs augments total α7 subunit expression in PC12 cells, which express endogenous α7 nAChRs. Transfection with α7 (α7+) increased the immunoreactive α7 signal by over 60% from endogenous mock-transfected control cells, whereas transfection with the mutant α7345–348A increased the total α7 signal by 48% over the endogenous α7 from control cells (Fig. 3A). PubMed:26088141

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MeSH
PC12 Cells

p(HGNC:CHRNA7) increases complex(p(HGNC:CHRNA7), p(HGNC:GNAQ)) View Subject | View Object

An increase in G protein association within the α7 complex was observed in α7+ cells (Gαq +16.71%; Gβγ +19.90%) (Fig. 3A). Similar findings in transfected N2a cells indicate a loss in G protein association within the α7 complex when α7345–348A nAChRs are expressed (Fig. 3B). PubMed:26088141

Appears in Networks:

p(HGNC:CHRNA7) increases complex(p(FPLX:"G_beta"), p(FPLX:"G_gamma"), p(HGNC:CHRNA7)) View Subject | View Object

An increase in G protein association within the α7 complex was observed in α7+ cells (Gαq +16.71%; Gβγ +19.90%) (Fig. 3A). Similar findings in transfected N2a cells indicate a loss in G protein association within the α7 complex when α7345–348A nAChRs are expressed (Fig. 3B). PubMed:26088141

Appears in Networks:

p(HGNC:CHRNA7) increases complex(p(HGNC:APP), p(HGNC:CHRNA7)) View Subject | View Object

Despite a putative beneficial role for increased CBF neuron alpha7 nAChR expression in AD (that may also be relevant to smoking behavior), evidence suggests that increased alpha7 nAChR expression contributes to cellular degeneration. Notably, alpha7 nAChR binds and/or interacts with APP and Ab peptides [123–125]. Increased NB neuronal alpha7 nAChR expression may arise as a compensatory response that is offset by aberrant Ab-alpha7 nAChR interactions, leading to cholinergic dysfunction. PubMed:18986241

Appears in Networks:
Annotations
Disease Ontology (DO)
Alzheimer's disease
MeSH
Cognitive Dysfunction

p(HGNC:CHRNA7) increases complex(a(CHEBI:"amyloid-beta"), p(HGNC:CHRNA7)) View Subject | View Object

Despite a putative beneficial role for increased CBF neuron alpha7 nAChR expression in AD (that may also be relevant to smoking behavior), evidence suggests that increased alpha7 nAChR expression contributes to cellular degeneration. Notably, alpha7 nAChR binds and/or interacts with APP and Ab peptides [123–125]. Increased NB neuronal alpha7 nAChR expression may arise as a compensatory response that is offset by aberrant Ab-alpha7 nAChR interactions, leading to cholinergic dysfunction. PubMed:18986241

Appears in Networks:
Annotations
Disease Ontology (DO)
Alzheimer's disease
MeSH
Cognitive Dysfunction

p(HGNC:CHRNA7) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

A decrease in the protein levels of the alpha3 and alpha4 nAChR subunits was recently measured in the temporal cortex and of the alpha3, alpha4, and alpha7 nAChR subtypes in the hippocampi of AD brains relative to age-matched control subjects (Guan et al 2000b) PubMed:11230871

Appears in Networks:
Annotations
MeSH
Hippocampus

p(HGNC:CHRNA7) hasVariant p(HGNC:CHRNA7, frag("231_255")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7) hasVariant p(HGNC:CHRNA7, frag("262_280")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7) hasVariant p(HGNC:CHRNA7, frag("470_490")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA7) positiveCorrelation bp(GO:cognition) View Subject | View Object

in the cerebral cortex, the massive reduction in nAChRs in Alzheimer’s disease128–130 involves predominantly the alpha4beta2 subtype, sparing the alpha7 subtype131. By contrast, in the hippocampus, a loss of alpha7 nAChRs seems to predominate and to correlate with the progressive loss of cognitive function132–136. PubMed:19721446

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease
Text Location
Review

act(p(HGNC:CHRNA7)) increases bp(GO:cognition) View Subject | View Object

First, there is a high level of expression of alpha7 nAChRs in the hippocampus, a region that is known to be involved in memory formation. Second, gene knockout and antisense studies have shown a role for alpha7 nAChRs in learning and memory144–146, and specifically in attention and working–episodic memory147,148. Third, pharmacological studies have shown that a range of structurally diverse alpha7 nAChR-selective agonists or positive allosteric modulators improve the cognitive deficits that are associated with Alzheimer’s disease. PubMed:19721446

Appears in Networks:
Annotations
MeSH
Alzheimer Disease
Text Location
Review

p(HGNC:CHRNA7) association a(MESH:Hippocampus) View Subject | View Object

First, there is a high level of expression of alpha7 nAChRs in the hippocampus, a region that is known to be involved in memory formation. Second, gene knockout and antisense studies have shown a role for alpha7 nAChRs in learning and memory144–146, and specifically in attention and working–episodic memory147,148. Third, pharmacological studies have shown that a range of structurally diverse alpha7 nAChR-selective agonists or positive allosteric modulators improve the cognitive deficits that are associated with Alzheimer’s disease. PubMed:19721446

Appears in Networks:
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Text Location
Review

p(HGNC:CHRNA7) association bp(GO:memory) View Subject | View Object

First, there is a high level of expression of alpha7 nAChRs in the hippocampus, a region that is known to be involved in memory formation. Second, gene knockout and antisense studies have shown a role for alpha7 nAChRs in learning and memory144–146, and specifically in attention and working–episodic memory147,148. Third, pharmacological studies have shown that a range of structurally diverse alpha7 nAChR-selective agonists or positive allosteric modulators improve the cognitive deficits that are associated with Alzheimer’s disease. PubMed:19721446

Appears in Networks:
Annotations
Text Location
Review

act(p(HGNC:CHRNA7)) decreases bp(GO:memory) View Subject | View Object

By contrast, deleting the alpha7 nAChR subunit in a mouse model of Alzheimer’s disease that overexpresses a mutated form of the human amyloid precursor protein confers protection against memory loss and synaptic dysfunction, supporting a crucial role for alpha7 nAChR as a target288. PubMed:19721446

Appears in Networks:
Annotations
MeSH
Alzheimer Disease
Text Location
Review

p(HGNC:CHRNA7) association bp(GO:learning) View Subject | View Object

First, there is a high level of expression of alpha7 nAChRs in the hippocampus, a region that is known to be involved in memory formation. Second, gene knockout and antisense studies have shown a role for alpha7 nAChRs in learning and memory144–146, and specifically in attention and working–episodic memory147,148. Third, pharmacological studies have shown that a range of structurally diverse alpha7 nAChR-selective agonists or positive allosteric modulators improve the cognitive deficits that are associated with Alzheimer’s disease. PubMed:19721446

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:CHRNA7) association bp(MESH:Neuroprotection) View Subject | View Object

The alpha7 nAChR has previously been implicated in the in vitro neuroprotective effects of nicotine, using PC12 cells151. PubMed:19721446

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
PC12
Text Location
Review

act(p(HGNC:CHRNA7)) decreases bp(MESH:Neuroprotection) View Subject | View Object

By contrast, deleting the alpha7 nAChR subunit in a mouse model of Alzheimer’s disease that overexpresses a mutated form of the human amyloid precursor protein confers protection against memory loss and synaptic dysfunction, supporting a crucial role for alpha7 nAChR as a target288. PubMed:19721446

Appears in Networks:
Annotations
MeSH
Alzheimer Disease
Text Location
Review

p(HGNC:CHRNA7) association bp(MESH:"Sensory Gating") View Subject | View Object

in addition, a decrease in alpha7 nAChR density in the hippocampus of patients with schizophrenia has been reported177. Similarly, a low density of alpha7 nAChRs in inbred strains of mice is associated with poor gating178. Recently, the expression of a novel variant of alpha7 nAChR, CHRNA7-2 (cholinergic receptor, nicotinic, alpha7, variant 2), was found to be reduced below control levels in the prefrontal cortex of patients with schizophrenia179. PubMed:19721446

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Text Location
Review

p(HGNC:CHRNA7) association a(CHEBI:clozapine) View Subject | View Object

However, the atypical antipsychotic drug clozapine normalizes auditory gating in DBA/2 mice — an effect which involves an alpha7 nAChR mechanism181. PubMed:19721446

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Text Location
Review

p(HGNC:CHRNA7) increases bp(GO:"neurotransmitter secretion") View Subject | View Object

α7 AChRs can act at the presynaptic, postsynaptic or perisynaptic levels to facilitate the liberation of neurotransmitters, mediate synaptic transmission, or modulate the connections of different neurons by activating diverse second messenger routes [1,19,23–31]. PubMed:22040696

Appears in Networks:

p(HGNC:CHRNA7) regulates bp(GO:"chemical synaptic transmission") View Subject | View Object

α7 AChRs can act at the presynaptic, postsynaptic or perisynaptic levels to facilitate the liberation of neurotransmitters, mediate synaptic transmission, or modulate the connections of different neurons by activating diverse second messenger routes [1,19,23–31]. PubMed:22040696

Appears in Networks:

p(HGNC:CHRNA7) regulates bp(GO:"neuron-neuron synaptic transmission") View Subject | View Object

α7 AChRs can act at the presynaptic, postsynaptic or perisynaptic levels to facilitate the liberation of neurotransmitters, mediate synaptic transmission, or modulate the connections of different neurons by activating diverse second messenger routes [1,19,23–31]. PubMed:22040696

Appears in Networks:

p(HGNC:CHRNA7) association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

AChRs have been linked to many neurodegenerative disorders [13,47–60]. PubMed:22040696

Appears in Networks:

p(HGNC:CHRNA7) association p(HGNC:BDNF) View Subject | View Object

BDNF can also influence the level of α7 AChRs subunits (Fig. 4) in the hippocampus and other brain regions [160,164,165]. PubMed:22040696

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Hippocampus

tloc(p(HGNC:CHRNA7), fromLoc(GO:"cell surface"), toLoc(GO:endosome)) increases act(p(HGNC:CREB1), ma(tscript)) View Subject | View Object

Additionally, SNARE-dependent trafficking was required for α7 AChRs to be capable of activating the transcription factor cAMP response element-binding protein and attendant gene ex- pression when challenged. PubMed:22040696

Appears in Networks:

p(HGNC:CHRNA7) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Reduction of α7 AChRs in the CNS is linked with Alzheimer dis- ease, which has been shown to lead to neuronal loss [53,188–190]. PubMed:22040696

Appears in Networks:
Annotations
MeSH
Central Nervous System

p(HGNC:CHRNA7) negativeCorrelation path(MESH:Schizophrenia) View Subject | View Object

Decreased expression of α7 AChR has also been associated with schizophrenia [51,195–197]. PubMed:22040696

Appears in Networks:
Annotations
MeSH
Hippocampus

p(HGNC:CHRNA7) increases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:Cytoplasm)) View Subject | View Object

Since α7 AChRs are highly permeable to calcium [198] and increased calcium permeability is required for neuronal migration [199], neurons with less α7 AChRs would fail to migrate to their correct destinations [200] and be activated by acetylcholine. PubMed:22040696

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Hippocampus

p(HGNC:CHRNA7) decreases path(MESH:"Renal Insufficiency") View Subject | View Object

During acute in- flammatory processes α7 AChRs attenuate renal failure induced by ische- mia/reperfusion by inhibiting pro-inflammatory cytokine expression, and subsequently decreasing cell apoptosis [180,201]. PubMed:22040696

Appears in Networks:
Annotations
MeSH
Inflammation

p(HGNC:CHRNA7) decreases bp(GO:"cytokine production") View Subject | View Object

During acute in- flammatory processes α7 AChRs attenuate renal failure induced by ische- mia/reperfusion by inhibiting pro-inflammatory cytokine expression, and subsequently decreasing cell apoptosis [180,201]. PubMed:22040696

Appears in Networks:
Annotations
MeSH
Inflammation

p(HGNC:CHRNA7) decreases bp(GO:"apoptotic process") View Subject | View Object

During acute in- flammatory processes α7 AChRs attenuate renal failure induced by ische- mia/reperfusion by inhibiting pro-inflammatory cytokine expression, and subsequently decreasing cell apoptosis [180,201]. PubMed:22040696

Appears in Networks:
Annotations
MeSH
Inflammation

p(HGNC:CHRNA7) association path(MESH:Neoplasms) View Subject | View Object

In addition, various studies have shown the expression of α7 nAChR (as mRNA and protein), in many different cancer cells obtained from human tumours. PubMed:28901280

Appears in Networks:
Annotations
MeSH
GABAergic Neurons

p(HGNC:CHRNA7) regulates bp(MESH:"Cell Survival") View Subject | View Object

α7-containing receptors are expressed in neurons and non-excitable cells in order to mediate pro-proliferative, sur- vival and anti-inflammatory signalling. PubMed:28901280

Appears in Networks:
Annotations
MeSH
GABAergic Neurons

p(HGNC:CHRNA7) regulates path(MESH:Inflammation) View Subject | View Object

α7-containing receptors are expressed in neurons and non-excitable cells in order to mediate pro-proliferative, sur- vival and anti-inflammatory signalling. PubMed:28901280

Appears in Networks:
Annotations
MeSH
GABAergic Neurons

p(HGNC:CHRNA7) increases bp(GO:"intracellular receptor signaling pathway") View Subject | View Object

it has recently been shown that the intra- cellular loop of the α7 subunit contains a G protein binding cluster that promotes intracellular signalling PubMed:28901280

Appears in Networks:
Annotations
MeSH
GABAergic Neurons

p(HGNC:CHRNA7) increases bp(GO:"JAK-STAT cascade") View Subject | View Object

whereas those on microglia increase intracellular calcium levels and signalling cascades without using channel function, and those on macrophages and other immunological cells signal through the JAK2/STAT3 tran- scription factor pathway PubMed:28901280

Appears in Networks:
Annotations
MeSH
GABAergic Neurons

p(HGNC:CHRNA7) regulates act(a(GO:synapse)) View Subject | View Object

acr-14 controls body movement by modulating the synaptic inputs and outputs of the ventral cord neural circuitry (83). PubMed:29191965

Appears in Networks:

p(HGNC:CHRNA7) regulates bp(GO:"musculoskeletal movement") View Subject | View Object

acr-14 controls body movement by modulating the synaptic inputs and outputs of the ventral cord neural circuitry (83). PubMed:29191965

Appears in Networks:

p(HGNC:CHRNA7) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

AD brains show an upregulation of CHRNA7 (acr-14 homolog in humans) (84), where it may mediate the Ab-induced tau pathology (85). PubMed:29191965

Appears in Networks:
Annotations
MeSH
Brain

p(HGNC:CHRNA7) regulates act(a(CHEBI:"amyloid-beta")) View Subject | View Object

AD brains show an upregulation of CHRNA7 (acr-14 homolog in humans) (84), where it may mediate the Ab-induced tau pathology (85). PubMed:29191965

Appears in Networks:
Annotations
MeSH
Brain

p(HGNC:CHRNA7) association path(MESH:Tauopathies) View Subject | View Object

Some of these enhancer genes are specific only to the tau-induced disease phenotype and include genes encoding proteins like WNT2 (111), TTBK2 (112), GSK-3b (113), TAOK1 (114, 115), CTSE (116) and CHRNA7 (117), have been implicated in tau-mediated pathology. PubMed:29191965

Appears in Networks:

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.