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a(CHEBI:"calcium(2+)")

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Entity

Name
calcium(2+)
Namespace
chebi
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/chebi-names.belns

Appears in Networks 24

FK506-Binding Protein 12.6/1b, a Negative Regulator of [Ca2], Rescues Memory and Restores Genomic Regulation in the Hippocampus of Aging Rats v1.0.0

Amyloid β oligomers (AβOs) in Alzheimer’s disease v1.0.0

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

Interplay of neurotransmitters in Alzheimer's disease 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

Neural Systems Governed by Nicotinic Acetylcholine Receptors: Emerging Hypotheses 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

Naturally-expressed nicotinic acetylcholine receptor subtypes v1.0.0

Alpha-synuclein oligomers: a new hope v1.0.0

Structural and functional properties of prefibrillar α-synuclein oligomers v1.0.0

Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing v1.0.0

Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease v1.0.0

Tau oligomers-Cytotoxicity, propagation, and mitochondrial damage v1.0.0

Tau oligomers-Cytotoxicity, propagation, and mitochondrial damage from Shafiei et al., 2017

TAU and Interaction Partners v1.2.5

TAU Interactions Section of NESTOR

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

Activation and regulation of the inflammasomes v1.0.0

Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NF-κB) - a Friend, a Foe, or a Bystander - in the Neurodegenerative Cascade and Pathogenesis of Alzheimer's Disease v1.0.0

In-Edges 56

p(MGI:Fkbp1b) decreases tloc(a(CHEBI:"calcium(2+)")) View Subject | View Object

Because FKBP1b is a negative regulator of hippocampal neuronal Ca2􏰅 transients PubMed:29255009

Appears in Networks:

a(HBP:HBP00023) increases a(CHEBI:"calcium(2+)") View Subject | View Object

It was demonstrated that Aβ42 oligomers, but not monomers, significantly altered Ca2+ release from intracellular stores (Lazzari et al. 2015), what induced intracellular Ca2+ increase in neurons via the complex PrPC–mGluR5, with harmful effects on synaptic transmission (Beraldo et al. 2016). PubMed:29196815

Appears in Networks:
Annotations
MeSH
Extracellular Space
Cell Ontology (CL)
neuron
Confidence
High
MeSH
Hippocampus

act(p(HGNC:GRIN1)) increases tloc(a(CHEBI:"calcium(2+)"), fromLoc(GO:"extracellular region"), toLoc(GO:"intracellular part")) View Subject | View Object

Excessive activation of NMDAR by soluble AβOs triggers disproportionate influx of Ca2+ into neurons, which leads to excitotoxicity, mitochondrial dysfunction, and loss of synapses (Zhao et al. 2004). PubMed:29196815

Appears in Networks:
Annotations
MeSH
Extracellular Space
Cell Ontology (CL)
neuron
Confidence
Medium

act(p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")) 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

Appears in Networks:
Annotations
MeSH
Muscles
MeSH
PC12 Cells
MeSH
Parasympathetic Nervous System
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

Appears in Networks:
Annotations
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

Appears in Networks:
Annotations
Text Location
Review

act(p(HBP:"alpha-3 beta-4 nAChR")) 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

Appears in Networks:
Annotations
Text Location
Review

a(CHEBI:nicotine) increases a(CHEBI:"calcium(2+)") 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

Appears in Networks:

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

Appears in Networks:

composite(a(CHEBI:"amyloid-beta"), p(HGNC:CHRNA7)) increases a(CHEBI:"calcium(2+)") View Subject | View Object

Stevens et al. (2003) showed that calcineurin is involved in nicotine neuroprotection. Abeta, through alpha7 nAChRs, increases Ca2+, which phosphorylates NMDARs via calcineurin and protein tyrosine phosphatase, nonreceptor type 5 (striatum-enriched) (Snyder et al., 2005). PubMed:19293145

Appears in Networks:

composite(a(CHEBI:"calcium(2+)"), a(MESH:Calcineurin), p(HGNC:PTPN5)) hasComponent a(CHEBI:"calcium(2+)") View Subject | View Object

Appears in Networks:

act(p(HGNCGENEFAMILY:"Inositol 1,4,5-triphosphate receptors")) association a(CHEBI:"calcium(2+)") 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

Appears in Networks:

tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) increases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Intracellular Space"), toLoc(GO:cytosol)) View Subject | View Object

This calcium influx can trigger calcium-induced calcium release from intracellular stores (86). PubMed:17009926

Appears in Networks:

act(p(FPLX:CHRN)) increases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

Nicotinic receptors mediate a small direct calcium influx (42–44, 85). PubMed:17009926

Appears in Networks:

p(HGNC:CHRNA7, var("p.Leu254Thr")) decreases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

Similarly, replacement of the α7 leucine at the synaptic, extracellular end (position 254 or 255) of the pore by threonine dramatically reduced the calcium permeability of the α7 receptors. PubMed:17009926

Appears in Networks:

p(HGNC:CHRNA7, var("p.Leu254Thr")) decreases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Intracellular Space"), toLoc(MESH:"Extracellular Space")) View Subject | View Object

Similarly, replacement of the α7 leucine at the synaptic, extracellular end (position 254 or 255) of the pore by threonine dramatically reduced the calcium permeability of the α7 receptors. PubMed:17009926

Appears in Networks:

p(HGNC:CHRNA7, var("p.Leu255Thr")) decreases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

Similarly, replacement of the α7 leucine at the synaptic, extracellular end (position 254 or 255) of the pore by threonine dramatically reduced the calcium permeability of the α7 receptors. PubMed:17009926

Appears in Networks:

p(HGNC:CHRNA7, var("p.Leu255Thr")) decreases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Intracellular Space"), toLoc(MESH:"Extracellular Space")) View Subject | View Object

Similarly, replacement of the α7 leucine at the synaptic, extracellular end (position 254 or 255) of the pore by threonine dramatically reduced the calcium permeability of the α7 receptors. PubMed:17009926

Appears in Networks:

p(FPLX:CHRN) increases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

All the mammalian neuronal nAChR subtypes do share the general func- tional property of being permeable to small monovalent and divalent cations. The main conducting species under biological conditions are Na+, K+, and Ca2+. PubMed:26472524

Appears in Networks:

p(FPLX:CHRN) increases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Intracellular Space"), toLoc(MESH:"Extracellular Space")) View Subject | View Object

All the mammalian neuronal nAChR subtypes do share the general func- tional property of being permeable to small monovalent and divalent cations. The main conducting species under biological conditions are Na+, K+, and Ca2+. PubMed:26472524

Appears in Networks:

act(a(MESH:"Receptors, Nicotinic")) increases tloc(a(CHEBI:"calcium(2+)"), fromLoc(GO:"extracellular region"), toLoc(GO:synapse)) View Subject | View Object

Stimulation of nicotinic receptors present at the CNS presynaptic neuronal membrane leads to an increase in presynaptic Ca2+ concentration, which may facilitate the release of a number of neurotransmitters, such as glutamate, GABA, dopamine, serotonin, norepinephrine, as well as ACh PubMed:26813123

Appears in Networks:
Annotations
MeSH
Central Nervous System
MeSH
Membranes
MeSH
Neurons

complex(a(CHEBI:"calcium(2+)"), p(GFAM:"Glutamate ionotropic receptor NMDA type subunits")) hasComponent a(CHEBI:"calcium(2+)") View Subject | View Object

Appears in Networks:

act(a(CHEBI:choline)) increases a(CHEBI:"calcium(2+)") View Subject | View Object

PC12 cells transfected with α7345–348A showed a reduction in choline-mediated calcium responses. PubMed:26088141

Appears in Networks:
Annotations
MeSH
PC12 Cells

a(CHEBI:nifedipine) decreases a(CHEBI:"calcium(2+)") View Subject | View Object

As shown in Fig. 5, A–C, nifedipine was found to decrease the peak calcium response to choline in PC12 cells (peak: 795.00% ΔF/Fθ ± 107.1%) by 56.94% (p = 0.003), whereas prolonging the duration of the choline-induced calcium transient (AUC: 749.50% ΔF/Fθ2 × s ± 64.02%) in the same cell. PubMed:26088141

Appears in Networks:
Annotations
MeSH
PC12 Cells

act(a(MESH:"Calcium Channels")) association a(CHEBI:"calcium(2+)") View Subject | View Object

In α7345–348A nAChR expressing cells, nifedipine had no effect on the peak or the duration of the calcium transient (peak: 957.00% ΔF/Fθ ± 252.2%; AUC: 333.33% ΔF/Fθ2 × s ± 91.53%) relative to choline treatment alone (Fig. 5, A–C). The findings suggest that choline-induced calcium responses in PC12 cells involve the activity of VGCC (37, 38). PubMed:26088141

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a(MESH:"GP Antagonist-2A peptide") causesNoChange a(CHEBI:"calcium(2+)") View Subject | View Object

SP pretreatment did not significantly alter calcium peaks in α7345–348A nAChR expressing cells, showing a small (−31.24%) reduction in calcium responses relative to the α7345–348A baseline measure (p > 0.05). PubMed:26088141

Appears in Networks:

p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) decreases a(CHEBI:"calcium(2+)") View Subject | View Object

PC12 cells transfected with α7345–348A showed a reduction in choline-mediated calcium responses. PubMed:26088141

Appears in Networks:
Annotations
MeSH
PC12 Cells

p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A")) decreases act(a(CHEBI:"calcium(2+)", loc(GO:intracellular))) View Subject | View Object

Xestospongin C treatment did not impact the calcium peak (628.87% ΔF/Fθ ± 69.43%) or total calcium transient (AUC: 443.86% ΔF/Fθ2 × s ± 54.72%; + xestospongin C = 340.39% ΔF/Fθ2 × s ± 96.99%) in α7345–348A expressing cells (α7 to α7 + xestospongin C, p = 0.017; α7 to α7345–348A, p = 0.013; α7 to α7345-348A + xestospongin C, p = 0.017) (Fig. 7, B and C). The data underscores the inability of α7345–348A nAChRs to activate intracellular calcium via IP3Rs (18). PubMed:26088141

Appears in Networks:

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

In α7+ cells, choline application resulted in a calcium signal that peaked at 1050% ΔF/Fθ (±176.4%) in the neurite. Calcium transients in the GC were found to last for ∼1.6 s in both α7 and α7+ cells peaking at 1396% (±154.4%) and 1316% (±146.9%) ΔF/Fθ, relatively (Fig. 4, A and B). PubMed:26088141

Appears in Networks:
Annotations
MeSH
Neurites

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

In N2a cells α7345–348A nAChR expression fostered a weak calcium response to (10 mM) choline, whereas expression of α7 nAChRs correlated with noticeable choline-induced calcium transient. Imaging studies in N2a cells expressing α7345–348A nAChRs indicate a significantly lowered calcium signal peak to choline (333.4% ΔF/Fθ ± 35.7%) when compared with N2a cells that express the α7nAChR (peak: 581% ΔF/Fθ ± 122.7%; p = 0.04) (Fig. 4, D and E). PubMed:26088141

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
Neuro-2a cell

composite(a(CHEBI:choline), p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A"))) decreases a(CHEBI:"calcium(2+)") View Subject | View Object

Most notably, in the GC, the calcium peak values were significantly lower in α7345–348A-transfected cells compared with α7 cells after Tukey's HSD post hoc comparisons (peak: 741 ± 159.8% ΔF/Fθ, p = 0.006). This represents a 46.92% reduction from the α7 baseline calcium response (Fig. 4, A and B). This reduction approached significance in the neurite of α7345–348A cells (peak: 561 ± 124.9% ΔF/Fθ) (Fig. 4, A and B) PubMed:26088141

Appears in Networks:
Annotations
MeSH
Neurites

composite(a(CHEBI:choline), p(HGNC:CHRNA7, var("p.345A"), var("p.346A"), var("p.347A"), var("p.348A"))) decreases a(CHEBI:"calcium(2+)") View Subject | View Object

In N2a cells α7345–348A nAChR expression fostered a weak calcium response to (10 mM) choline, whereas expression of α7 nAChRs correlated with noticeable choline-induced calcium transient. Imaging studies in N2a cells expressing α7345–348A nAChRs indicate a significantly lowered calcium signal peak to choline (333.4% ΔF/Fθ ± 35.7%) when compared with N2a cells that express the α7nAChR (peak: 581% ΔF/Fθ ± 122.7%; p = 0.04) (Fig. 4, D and E). PubMed:26088141

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
Neuro-2a cell

a(HBP:"S 24795") increases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

The incubation with S 24795 was able to normalize Ca++ influx mediated by both alpha7 nAChR and NMDAR (Wang et al., 2009, 2010) PubMed:25514383

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(MESH:"Receptors, N-Methyl-D-Aspartate") regulates tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

The incubation with S 24795 was able to normalize Ca++ influx mediated by both alpha7 nAChR and NMDAR (Wang et al., 2009, 2010) PubMed:25514383

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(MESH:"alpha7 Nicotinic Acetylcholine Receptor") increases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

In a different study, rat hippocampus and cortex were investigated and the activation of both alpha7 and non-alpha7 receptors was obtained with an enhancement of Ca++ influx into the neuron following the application of picomolar (pM) concentrations of Abeta1-42 PubMed:25514383

Appears in Networks:

act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) regulates tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

The incubation with S 24795 was able to normalize Ca++ influx mediated by both alpha7 nAChR and NMDAR (Wang et al., 2009, 2010) PubMed:25514383

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

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

This kinase is sensitive to Ca++, whose levels are increased following nAChR activation (Oddo et al., 2005) PubMed:25514383

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(MGI:Lynx1) decreases a(CHEBI:"calcium(2+)") View Subject | View Object

As a consequence of nAChR hypersensitivity, lynx1 knockout mice display increased levels of Ca2+ in neurons, enhancements in synaptic efficacy, and improved learning and memory functions (Miwa et al., 2006; Darvas et al., 2009; Tekinay et al., 2009) PubMed:21482353

Appears in Networks:
Annotations
MeSH
Neurons

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

a(HBP:"alpha-7-containing nAChR") decreases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

Subsequently, renewed searches for functions of natural Bgt-binding nAChRs uncovered short-lived, nicotine-gated, toxin-sensitive, inward currents and/ or elevations of intracellular Ca2+ in chick autonomic neurons [84], in human ganglionic neuron-like clonal cells [85], or in rat CNS neurons [16,40–44,86–91]. PubMed:21787755

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron

a(HBP:HBP00093) increases tloc(a(CHEBI:"calcium(2+)"), fromLoc(GO:"extracellular space"), toLoc(GO:"intracellular part")) View Subject | View Object

Dysfunctional membranes can also have an important impact on calcium homeostasis; some types of oligomers can lead to a cytotoxic calcium influx presumably by building pore-like structures [30]. PubMed:28803412

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Microglia

a(HBP:HBP00092) increases a(CHEBI:"calcium(2+)") View Subject | View Object

1 nM (Fig. 3a, right panels and Fig. 3b, red curve, solid line) and 0.2 nM α -syn fibrils (Fig. 3b, red curve, dashed line) induced a progressive and significant increase of intracellular Ca2+ levels, as revealed by the rise of Fluo-4 fluorescence in exposed SH-SY5Y cells. In contrast, only a modest Ca2+ increase was observed in cells exposed to 300 nM on-fibrillar assembly pathway oligomeric α -syn (Fig. 3a, middle panels and Fig. 3b, blue curve, solid line) or 10 μM monomeric α -syn (Fig. 3a, left panels and Fig. 3b, black curve, solid line). PubMed:27075649

Appears in Networks:
Annotations
MeSH
Intracellular Space
Cell Ontology (CL)
neuron
Confidence
Medium
MeSH
Lewy Bodies

a(HBP:HBP00093) increases a(CHEBI:"calcium(2+)") View Subject | View Object

1 nM (Fig. 3a, right panels and Fig. 3b, red curve, solid line) and 0.2 nM α -syn fibrils (Fig. 3b, red curve, dashed line) induced a progressive and significant increase of intracellular Ca2+ levels, as revealed by the rise of Fluo-4 fluorescence in exposed SH-SY5Y cells. In contrast, only a modest Ca2+ increase was observed in cells exposed to 300 nM on-fibrillar assembly pathway oligomeric α -syn (Fig. 3a, middle panels and Fig. 3b, blue curve, solid line) or 10 μM monomeric α -syn (Fig. 3a, left panels and Fig. 3b, black curve, solid line). PubMed:27075649

Appears in Networks:
Annotations
MeSH
Intracellular Space
Cell Ontology (CL)
neuron
Confidence
Medium
MeSH
Lewy Bodies

composite(a(CHEBI:"calcium(2+)"), p(HGNC:CAMKK2)) hasComponent a(CHEBI:"calcium(2+)") View Subject | View Object

Appears in Networks:

act(p(HGNC:MCOLN1)) increases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:Lysosomes), toLoc(MESH:Cytoplasm)) View Subject | View Object

Fourth, activation of the lysosomal Ca 2+ channel mucol- ipin transient receptor potential channel 1 (TRPML1) with a synthetic agonist (ML-SA1) increased lysoso- mal Ca 2+ release, lowered pH and promoted Aβ clear- ance 191,192 . PubMed:30116051

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bp(HBP:Excitotoxicity) increases a(CHEBI:"calcium(2+)", loc(GO:intracellular)) View Subject | View Object

Excitotoxicity leading to elevated intracellular calcium is a common feature of neurodegenerative diseases, and is implicated in AD (49, 50). This process may lead to enhanced activation of calpains (51). This in turn could influence a number of pathologic processes, including tau proteolysis. Indeed, tau has a number of putative calpain cleavage sites, and incubation of recombinant tau with calpain generates specific fragments, including one that is ∼35 kDa and one that is ∼17 kDa (19, 20). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Alzheimer Disease
MeSH
Neurodegenerative Diseases
Text Location
Review

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

Tau may be endocytosed, promoting an increase in intracellular calcium that results in neuronal death PubMed:28420982

Appears in Networks:
Annotations
MeSH
Intracellular Space
Confidence
Medium
MeSH
Exosomes
MeSH
Alzheimer Disease

complex(a(CHEBI:"calcium(2+)"), p(FPLX:CALM)) hasComponent a(CHEBI:"calcium(2+)") View Subject | View Object

Appears in Networks:

complex(a(CHEBI:"calcium(2+)"), p(FPLX:CALM), p(HGNC:MAPT)) hasComponent a(CHEBI:"calcium(2+)") View Subject | View Object

Appears in Networks:

a(HBP:maitotoxin) increases a(CHEBI:"calcium(2+)") View Subject | View Object

For these studies, SH-SY5Y cells stably overexpressing tTG were used. tTG coimmunoprecipitated with tau, and elevating intracellular calcium levels with maitotoxin resulted in a 52 +/- 4% increase in the amount of tTG that coimmunoprecipitated with tau. The increase in association of tTG with tau after treatment with maitotoxin corresponded to a coimmunolocalization of tTG, tTG activity, and tau in the cells. Further, tau was modified by tTG in situ in response to maitotoxin treatment. In vitro polyaminated tau was significantly less susceptible to micro-calpain proteolysis; however, tTG-mediated polyamination of tau did not significantly alter the microtubule-binding capacity of tau. PubMed:10537045

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bp(MESH:"Oxidative Stress") increases a(CHEBI:"calcium(2+)") View Subject | View Object

Only middle-aged Tet-mev-1 mice showed JNK/MARK activation and Ca2+ overload, particularly in astrocytes with decreased hippocampal GFAP and S100ß, but without pathological features such as apoptosis, amyloidosis, and lactic acidosis in neurons and astrocytes. This led to decreasing levels of glial fibrillary acidic protein and S100β in the hippocampal area. PubMed:27623715

Appears in Networks:
Annotations
Uberon
hippocampal formation
Cell Ontology (CL)
astrocyte

complex(p(HGNC:MAPT), p(HGNC:TGM2)) positiveCorrelation a(CHEBI:"calcium(2+)") View Subject | View Object

For these studies, SH-SY5Y cells stably overexpressing tTG were used. tTG coimmunoprecipitated with tau, and elevating intracellular calcium levels with maitotoxin resulted in a 52 +/- 4% increase in the amount of tTG that coimmunoprecipitated with tau. The increase in association of tTG with tau after treatment with maitotoxin corresponded to a coimmunolocalization of tTG, tTG activity, and tau in the cells. Further, tau was modified by tTG in situ in response to maitotoxin treatment. In vitro polyaminated tau was significantly less susceptible to micro-calpain proteolysis; however, tTG-mediated polyamination of tau did not significantly alter the microtubule-binding capacity of tau. PubMed:10537045

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p(HGNC:DDIT3) regulates a(CHEBI:"calcium(2+)") View Subject | View Object

Another regulator of Ca2+, namely C/EPB-homologous protein (CHOP; also known as DDIT3), has been implicated in NLRP3 inflammasome activation89 PubMed:23702978

Appears in Networks:
Annotations
Confidence
High
MeSH
Extracellular Space
NeuroMMSigDB
Caspase subgraph

p(HGNC:MAP3K7) association a(CHEBI:"calcium(2+)") View Subject | View Object

The mobilized Ca2+ has many molecular targets, including TGFβ-activated kinase 1 (TAK1; also known as MAP3K7) (REF. 86). PubMed:23702978

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Confidence
High
MeSH
Extracellular Space

act(p(HGNC:TRPM2)) increases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

This channel senses intracellular ROS and responds by opening itself to facilitate Ca2+ influx into the cell; this is intriguing considering that both ion fluxes and the oxidative state (see below) have important roles in NLRP3 inflammasome activation. PubMed:23702978

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Confidence
High
MeSH
Extracellular Space
NeuroMMSigDB
Caspase subgraph

a(CHEBI:"amyloid-beta") increases a(CHEBI:"calcium(2+)") View Subject | View Object

Emerging evidence has implicated Amyloid-β in augmenting cytosolic Ca2+ levels and causing NF- κB activation via calcineurin in astrocytes PubMed:28745240

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MeSH
Cytosol
MeSH
Alzheimer Disease

Out-Edges 30

a(CHEBI:"calcium(2+)", loc(GO:intracellular)) increases act(p(FPLX:CREB), ma(tscript)) 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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Review

a(CHEBI:"calcium(2+)", loc(GO:intracellular)) 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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MeSH
Neurons
Text Location
Review

a(CHEBI:"calcium(2+)", loc(GO:intracellular)) regulates bp(GO:"signal release") View Subject | View Object

It was then recognized that Ca2+ flux directly through nAChR channels or indirectly via voltage-gated Ca2+ channels is relevant for nicotinic modulation of transmitter release, synaptic plasticity, as well as neuronal viability, differentiation, and migration. PubMed:19126755

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Review

a(CHEBI:"calcium(2+)", loc(GO:intracellular)) regulates bp(MESH:"Neuronal Plasticity") View Subject | View Object

It was then recognized that Ca2+ flux directly through nAChR channels or indirectly via voltage-gated Ca2+ channels is relevant for nicotinic modulation of transmitter release, synaptic plasticity, as well as neuronal viability, differentiation, and migration. PubMed:19126755

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Review

a(CHEBI:"calcium(2+)", loc(GO:intracellular)) regulates bp(GO:"neuron migration") View Subject | View Object

It was then recognized that Ca2+ flux directly through nAChR channels or indirectly via voltage-gated Ca2+ channels is relevant for nicotinic modulation of transmitter release, synaptic plasticity, as well as neuronal viability, differentiation, and migration. PubMed:19126755

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Review

a(CHEBI:"calcium(2+)", loc(GO:intracellular)) regulates bp(GO:"neuron differentiation") View Subject | View Object

It was then recognized that Ca2+ flux directly through nAChR channels or indirectly via voltage-gated Ca2+ channels is relevant for nicotinic modulation of transmitter release, synaptic plasticity, as well as neuronal viability, differentiation, and migration. PubMed:19126755

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Text Location
Review

a(CHEBI:"calcium(2+)") association act(p(HGNCGENEFAMILY:"Inositol 1,4,5-triphosphate 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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a(CHEBI:"calcium(2+)") increases act(p(MESH:"Receptors, Nicotinic")) View Subject | View Object

One group of modulators includes Ca2+􏰆, which potentiates most neuronal nAChRs (99, 100) and binds to the extracellular domain below the ACh site at residues contributed from both sides of the subunit interface (96). Another includes Zn2 􏰆 . PubMed:23038257

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tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) increases tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Intracellular Space"), toLoc(GO:cytosol)) View Subject | View Object

This calcium influx can trigger calcium-induced calcium release from intracellular stores (86). PubMed:17009926

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tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) increases bp(GO:"membrane depolarization") View Subject | View Object

While nAChR activity causes depolarization, the divalent cation permeability plays an impor- tant physiological role by supplying ionic signals, including calcium (Bertrand, Galzi, Devillers-Thiery, Bertrand, & Changeux, 1993b; Dani & Bertrand, 2007; Decker & Dani, 1990; Gray, Rajan, Radcliffe, Yakehiro, & Dani, 1996; McGehee, Heath, Gelber, Devay, & Role, 1995; Vernino et al., 1992). PubMed:26472524

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a(CHEBI:"calcium(2+)") regulates act(p(FPLX:CHRN)) View Subject | View Object

Although calcium modulation can act intracellularly, nAChRs also are allosterically modulated by extracellular calcium, leading to dramatic changes in the channel opening probability (Amador & Dani, 1995; Mulle, Lena, & Changeux, 1992; Vernino et al., 1992). PubMed:26472524

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MeSH
Extracellular Space

a(CHEBI:"calcium(2+)") increases tloc(a(CHEBI:"glutamate(2-)"), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Stimulation of nicotinic receptors present at the CNS presynaptic neuronal membrane leads to an increase in presynaptic Ca2+ concentration, which may facilitate the release of a number of neurotransmitters, such as glutamate, GABA, dopamine, serotonin, norepinephrine, as well as ACh PubMed:26813123

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MeSH
Synapses

a(CHEBI:"calcium(2+)") increases tloc(a(CHEBI:"gamma-aminobutyric acid"), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Stimulation of nicotinic receptors present at the CNS presynaptic neuronal membrane leads to an increase in presynaptic Ca2+ concentration, which may facilitate the release of a number of neurotransmitters, such as glutamate, GABA, dopamine, serotonin, norepinephrine, as well as ACh PubMed:26813123

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MeSH
Synapses

a(CHEBI:"calcium(2+)") increases tloc(a(CHEBI:dopamine), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Stimulation of nicotinic receptors present at the CNS presynaptic neuronal membrane leads to an increase in presynaptic Ca2+ concentration, which may facilitate the release of a number of neurotransmitters, such as glutamate, GABA, dopamine, serotonin, norepinephrine, as well as ACh PubMed:26813123

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MeSH
Synapses

a(CHEBI:"calcium(2+)") increases tloc(a(CHEBI:serotonin), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Stimulation of nicotinic receptors present at the CNS presynaptic neuronal membrane leads to an increase in presynaptic Ca2+ concentration, which may facilitate the release of a number of neurotransmitters, such as glutamate, GABA, dopamine, serotonin, norepinephrine, as well as ACh PubMed:26813123

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MeSH
Synapses

a(CHEBI:"calcium(2+)") increases tloc(a(CHEBI:noradrenaline), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Stimulation of nicotinic receptors present at the CNS presynaptic neuronal membrane leads to an increase in presynaptic Ca2+ concentration, which may facilitate the release of a number of neurotransmitters, such as glutamate, GABA, dopamine, serotonin, norepinephrine, as well as ACh PubMed:26813123

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MeSH
Synapses

a(CHEBI:"calcium(2+)") increases tloc(a(CHEBI:acetylcholine), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Stimulation of nicotinic receptors present at the CNS presynaptic neuronal membrane leads to an increase in presynaptic Ca2+ concentration, which may facilitate the release of a number of neurotransmitters, such as glutamate, GABA, dopamine, serotonin, norepinephrine, as well as ACh PubMed:26813123

Appears in Networks:
Annotations
MeSH
Synapses

a(CHEBI:"calcium(2+)") regulates p(FPLX:CHRN) View Subject | View Object

Moreover,nicotinic receptors can also be regulated allosterically by Ca2+ PubMed:26813123

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a(CHEBI:"calcium(2+)") association act(a(MESH:"Calcium Channels")) View Subject | View Object

In α7345–348A nAChR expressing cells, nifedipine had no effect on the peak or the duration of the calcium transient (peak: 957.00% ΔF/Fθ ± 252.2%; AUC: 333.33% ΔF/Fθ2 × s ± 91.53%) relative to choline treatment alone (Fig. 5, A–C). The findings suggest that choline-induced calcium responses in PC12 cells involve the activity of VGCC (37, 38). PubMed:26088141

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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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Review

a(CHEBI:"calcium(2+)") increases act(p(HBP:"alpha-4 beta-2 nAChR")) View Subject | View Object

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

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Review

tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:Cytoplasm)) increases bp(GO:"neuron migration") 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

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Cell Ontology (CL)
neuron
MeSH
Hippocampus

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

Calpains are calcium-activated cytosolic cysteine proteases. Two isoforms differentiated and named by their sensitivities to calcium (i.e., μ-calpain and m-calpain, also called calpain-1 and calpain-2) are abundant in the central nervous system, and respond to micromolar and millimolar concentrations of calcium, respectively (45). Calpain has been implicated in a number of neurodegenerative diseases [for a review, see (46)]. PubMed:24027553

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Review

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

Excitotoxicity leading to elevated intracellular calcium is a common feature of neurodegenerative diseases, and is implicated in AD (49, 50). This process may lead to enhanced activation of calpains (51). This in turn could influence a number of pathologic processes, including tau proteolysis. Indeed, tau has a number of putative calpain cleavage sites, and incubation of recombinant tau with calpain generates specific fragments, including one that is ∼35 kDa and one that is ∼17 kDa (19, 20). PubMed:24027553

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MeSH
Alzheimer Disease
MeSH
Neurodegenerative Diseases
Text Location
Review

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

Increasing intracellular calcium levels in PC12 cells leads to calpain-induced cleavage of tau (18). This may reflect a potential effect of excitotoxicity in AD. Inducing apoptosis in cerebellar granule cells yields calpain-mediated tau fragments, including a dominant ∼17 kDa fragment (17). PubMed:24027553

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Experimental Factor Ontology (EFO)
PC12
Text Location
Review

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

These findings provide new insights into the regulation of microtubule assembly, since Ca2+/calmodulin inhibition of tubulin polymerization into microtubules could be mediated by the direct binding of calmodulin to tau, thus preventing the interaction of this latter protein with tubulin. PubMed:2123288

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a(CHEBI:"calcium(2+)") increases act(p(HGNC:S100B)) View Subject | View Object

We here confirmed the interaction of SlOOb with tau through affinity chromatography and crosslinking and demonstrated that such an interaction also inhibited mode I phosphorylation by a Ca2+/CaM-dependent kinase. Increasing Ca2+c oncentration to the 100 μM range potentiated the SlOOb effect. Therefore, although Ca2+-independent interactions may occur between SlOOb and protein tau, it is the Ca2+ form of SlOOb that has significant affinity for protein tau. In any case, Znz+ and Ca2+ both appear to be capabble of inducing a conformation in SlOOb that promotes its binding to target proteinins, including tau. PubMed:2833519

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a(CHEBI:"calcium(2+)") positiveCorrelation complex(p(HGNC:MAPT), p(HGNC:TGM2)) View Subject | View Object

For these studies, SH-SY5Y cells stably overexpressing tTG were used. tTG coimmunoprecipitated with tau, and elevating intracellular calcium levels with maitotoxin resulted in a 52 +/- 4% increase in the amount of tTG that coimmunoprecipitated with tau. The increase in association of tTG with tau after treatment with maitotoxin corresponded to a coimmunolocalization of tTG, tTG activity, and tau in the cells. Further, tau was modified by tTG in situ in response to maitotoxin treatment. In vitro polyaminated tau was significantly less susceptible to micro-calpain proteolysis; however, tTG-mediated polyamination of tau did not significantly alter the microtubule-binding capacity of tau. PubMed:10537045

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a(CHEBI:"calcium(2+)") association p(HGNC:MAP3K7) View Subject | View Object

The mobilized Ca2+ has many molecular targets, including TGFβ-activated kinase 1 (TAK1; also known as MAP3K7) (REF. 86). PubMed:23702978

Appears in Networks:
Annotations
Confidence
High
MeSH
Extracellular Space

tloc(a(CHEBI:"calcium(2+)"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) increases act(p(HGNC:NLRP3)) View Subject | View Object

This channel senses intracellular ROS and responds by opening itself to facilitate Ca2+ influx into the cell; this is intriguing considering that both ion fluxes and the oxidative state (see below) have important roles in NLRP3 inflammasome activation. PubMed:23702978

Appears in Networks:
Annotations
Confidence
High
MeSH
Extracellular Space
NeuroMMSigDB
Caspase subgraph

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.