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p(HGNC:ACHE)

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Entity

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

Appears in Networks 10

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

Alzheimer's Disease: Targeting the Cholinergic System 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

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

Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer’s disease v1.0.0

In-Edges 27

a(CHEBI:donepezil) decreases p(HGNC:ACHE) View Subject | View Object

Drugs currently approved to treat mild-to-moderate AD, including galantamine, donepezil, and rivastigmine, all inhibit AChE, the enzyme that hydrolyzes ACh (462). PubMed:19126755

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Text Location
Review

a(CHEBI:galanthamine) decreases p(HGNC:ACHE) View Subject | View Object

Drugs currently approved to treat mild-to-moderate AD, including galantamine, donepezil, and rivastigmine, all inhibit AChE, the enzyme that hydrolyzes ACh (462). PubMed:19126755

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Text Location
Review

a(CHEBI:rivastigmine) decreases p(HGNC:ACHE) View Subject | View Object

Drugs currently approved to treat mild-to-moderate AD, including galantamine, donepezil, and rivastigmine, all inhibit AChE, the enzyme that hydrolyzes ACh (462). PubMed:19126755

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Text Location
Review

a(CHEBI:"EC 3.1.1.7 (acetylcholinesterase) inhibitor") decreases act(p(HGNC:ACHE)) View Subject | View Object

The most commonly prescribed treatments for AD are acetylcholinesterase inhibitors, which decrease the hydrolysis rate of ACh and, thereby, enhance cholinergic signaling. One such drug, galantamine (Reminyl), also potentiates nAChRs (66). PubMed:17009926

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Annotations
MeSH
Alzheimer Disease

a(CHEBI:"organophosphorus compound") decreases act(p(HGNC:ACHE)) View Subject | View Object

The organophosphate compounds are irreversible AChE inhibitors that are used as insecticides and nerve gases PubMed:26813123

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a(CHEBI:antidote) increases act(p(HGNC:ACHE)) View Subject | View Object

Thus, antidotes, including doxylamine, can be used to speed enzyme regeneration PubMed:26813123

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a(CHEBI:doxylamine) increases act(p(HGNC:ACHE)) View Subject | View Object

Thus, antidotes, including doxylamine, can be used to speed enzyme regeneration PubMed:26813123

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a(CHEBI:succinylcholine) decreases act(p(HGNC:ACHE)) View Subject | View Object

Moreover, AChE inhibitors that compete for the enzyme site, as succinylcholine, are used as anesthetic adjuvants since these drugs can promote neuromuscular blockage PubMed:26813123

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a(MESH:"Cholinergic Neurons") increases tloc(p(HGNC:ACHE), fromLoc(MESH:"Synaptic Vesicles"), toLoc(GO:"synaptic cleft")) View Subject | View Object

Cholinergic neurons secrete AChE into the synaptic cleft, where the enzyme is normally associated with the plasma membrane (see Fig. 1) PubMed:26813123

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complex(a(MESH:"Amyloid beta-Peptides"), p(HGNC:ACHE)) hasComponent p(HGNC:ACHE) View Subject | View Object

Appears in Networks:

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

Furthermore, some evidences also suggest the involvement of AChE in the pathogenesis of AD PubMed:26813123

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a(MESHC:latrepirdine) decreases act(p(HGNC:ACHE)) View Subject | View Object

Recently, the novel non-selective antihistamine dimebon (2,3,4,5-tetrahydro2,8-dimethyl-5–2[-6methyl 3-pyridnyl)ethyl]-1H-pyrido[4,3-b] indole) was shown to inhibit BChE and AChE, block the NMDA receptor signaling pathway, inhibit mitochondrial permeability and provide neuroprotective effects in models of AD [194]. PubMed:18986241

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Annotations
Disease Ontology (DO)
Alzheimer's disease
MeSH
Cognitive Dysfunction

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

Positron emission tomography studies have revealed a reduced cortical acetylcholinesteserase activity in AD patients (Iyo et al 1997; Kuhl et al 1999) PubMed:11230871

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MeSH
Cerebral Cortex

path(MESH:D000544) decreases p(HGNC:ACHE) View Subject | View Object

Specifically, progressive phenotypic downregulation of markers within CBF neurons as well as frank CBF cell loss has been observed consistently, along with an associated reduction of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity within the cortex in AD [16]. Most researchers presumed that progressive disruption of cholinergic function underlies much of the short-term memory loss seen in AD PubMed:18986241

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path(MESH:D000544) causesNoChange act(p(HGNC:ACHE)) View Subject | View Object

Butyrylcholinesterase (BChE) is a serine hydrolase similar to AChE that is widely distributed throughout the CNS and also catalyzes the hydrolysis of ACh. BChE is localized to neurons and glia, and is associated with NFTs and senile plaques (SPs) in AD brain [32]. Interestingly, population-based genetic studies of AD have identified a point mutation that changes Ala539 to threonine in the K variant of BChE, which effectively reduces serum BChE concentrations, and may be associated with cognitive decline [33]. BChE activity also increases in AD brain whereas AChE activity remains unchanged or declines [34,35]. PubMed:18986241

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Annotations
Disease Ontology (DO)
Alzheimer's disease
MeSH
Neuroglia
MeSH
Neurons
MeSH
Cognitive Dysfunction

path(MESH:D000544) decreases act(p(HGNC:ACHE)) View Subject | View Object

Butyrylcholinesterase (BChE) is a serine hydrolase similar to AChE that is widely distributed throughout the CNS and also catalyzes the hydrolysis of ACh. BChE is localized to neurons and glia, and is associated with NFTs and senile plaques (SPs) in AD brain [32]. Interestingly, population-based genetic studies of AD have identified a point mutation that changes Ala539 to threonine in the K variant of BChE, which effectively reduces serum BChE concentrations, and may be associated with cognitive decline [33]. BChE activity also increases in AD brain whereas AChE activity remains unchanged or declines [34,35]. PubMed:18986241

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

path(MESH:D000544) decreases act(p(HGNC:ACHE)) View Subject | View Object

For example, the vesicular ACh transporter (VAChT), which is co-expressed with ChAT in human CBF neurons and participates in loading ACh into synaptic vesicles in cholinergic terminals, is not severely altered in AD [40]. In this regard, pharmacological studies of VAChT in postmortem AD tissue or in vivo imaging studies using vesamicol and its analogs, suggest that VAChT levels remain steady or are minimally decreased coincident with a severe decline in ChAT activity in cortical areas [41]. PubMed:18986241

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Annotations
MeSH
Cognitive Dysfunction

path(MESH:D003704) decreases p(HGNC:ACHE) View Subject | View Object

The enzyme that hydrolyzes ACh at the synapse, AChE, does not show a decline in cortical areas until at least moderately severe levels of dementia [28]. PubMed:18986241

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path(MESH:D058225) association p(HGNC:ACHE) View Subject | View Object

In this regard, AChE has been localized to SPs in the vicinity of cholinergic synapses, and experimental evidence suggests that AChE promotes Ab fibrillization [164], suggesting that a further benefit from AChE inhibitor therapy may be to prevent continued Ab deposition in cholinergic projection sites. PubMed:18986241

Appears in Networks:
Annotations
MeSH
Cognitive Dysfunction

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

It is likely that the therapeutic benefit of cholinesterase inhibitors occurs at least in part through activation of the nAChRs, by the direct action of increased levels and/or through a direct activation of the allosteric site on the nAChR (Maelicke et al 1995, 2000) PubMed:11230871

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

It is likely that the therapeutic benefit of cholinesterase inhibitors occurs at least in part through activation of the nAChRs, by the direct action of increased levels and/or through a direct activation of the allosteric site on the nAChR (Maelicke et al 1995, 2000) PubMed:11230871

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a(CHEBI:rivastigmine) increases act(p(HGNC:ACHE)) View Subject | View Object

It is likely that the therapeutic benefit of cholinesterase inhibitors occurs at least in part through activation of the nAChRs, by the direct action of increased levels and/or through a direct activation of the allosteric site on the nAChR (Maelicke et al 1995, 2000) PubMed:11230871

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a(CHEBI:tacrine) increases act(p(HGNC:ACHE)) View Subject | View Object

It is likely that the therapeutic benefit of cholinesterase inhibitors occurs at least in part through activation of the nAChRs, by the direct action of increased levels and/or through a direct activation of the allosteric site on the nAChR (Maelicke et al 1995, 2000) PubMed:11230871

Appears in Networks:

a(CHEBI:tacrine) increases act(p(HGNC:ACHE)) View Subject | View Object

Since an enhanced activity of acetylcholinesterase has been measured in cerebrospinal fluid following long-term treatment with tacrine (Nordberg et al 1999), possibly as a result of an increased acetylcholinesterase gene expression, it might be an advantage to use drugs interacting with nAChRs PubMed:11230871

Appears in Networks:
Annotations
MeSH
Cerebrospinal Fluid

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

A progressive loss of cortical acetylcholinesterase activity has been observed in AD patients with cognitive decline (Shinotoh et al 2000) PubMed:11230871

Appears in Networks:
Annotations
MeSH
Cerebral Cortex

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

The loss in cortical acetylcholinesterase activity was less pronounced in mildly demented AD patients relative to autopsy material and did not strictly correlate with cerebral glucose metabolism impairment (Kuhl et al 1999) PubMed:11230871

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a(CHEBI:galanthamine) decreases act(p(HGNC:ACHE)) View Subject | View Object

It inhibits AChE competitively and reversibly, causing elevated cerebral concen-trations of ACh, and thus, enhancing cholinergic activity. PubMed:29179999

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Out-Edges 15

p(HGNC:ACHE) decreases act(a(CHEBI:nicotine)) View Subject | View Object

At the neuromuscular junction, nicotinic function is enhanced by inhibition of acetylcholinesterase (AChE), the enzyme that metabolizes the endogenous neurotransmitter ACh. PubMed:19126755

Appears in Networks:
Annotations
MeSH
Neuromuscular Junction
Text Location
Review

p(HGNC:ACHE) decreases a(CHEBI:acetylcholine) View Subject | View Object

Several lines of evidence point to a link between brain nAChRs and the development of AD. Biochemical analysis of brains of patients with AD reveals deficits in nAChRs, an increase in butyrylcholinesterase, reduction in ACh, and attenuated activity of cholinergic synthetic [choline acetyltransferase (ChAT)] and inactivating (AChE) enzymes (Bartus et al., 1982; Francis et al., 1999).Butyrylcholinesterase and AChE help terminate ACh signaling by hydrolyzing the transmitter, thereby inactivating it. PubMed:19293145

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p(HGNC:ACHE) increases act(a(CHEBI:chlorpromazine)) View Subject | View Object

The kinetics of access of chlorpromazine to this site increased by 100-fold when rap- idly mixed with ACh under conditions expected to generate functional ion channels PubMed:23038257

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act(p(HGNC:ACHE), ma(pep)) directlyIncreases deg(a(CHEBI:acetylcholine)) View Subject | View Object

Unlike many neurotransmitter signals that are shaped by pumps that return the transmitter to the intracellular space, the spread of ACh from the release site is determined by diffusion and by acetylcholinesterase (AChE) hydrolysis of ACh. PubMed:17009926

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act(p(HGNC:ACHE), ma(pep)) directlyIncreases rxn(reactants(a(CHEBI:acetylcholine)), products(a(CHEBI:acetate), a(CHEBI:choline))) View Subject | View Object

Another important aspect of this diffusive ACh signal is that its eventual hydrolysis creates choline, which also activates and desensitizes nAChRs in a subtype-selective manner (54, 55). PubMed:17009926

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p(HGNC:ACHE) decreases act(a(CHEBI:acetylcholine)) View Subject | View Object

ACh present at the synaptic cleft is rapidly inactivated by the enzyme acetylcholinesterase (AChE), releasing choline and acetate PubMed:26813123

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p(HGNC:ACHE) increases rxn(reactants(a(CHEBI:acetylcholine)), products(a(CHEBI:acetate), a(CHEBI:choline))) View Subject | View Object

ACh present at the synaptic cleft is rapidly inactivated by the enzyme acetylcholinesterase (AChE), releasing choline and acetate PubMed:26813123

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

Furthermore, some evidences also suggest the involvement of AChE in the pathogenesis of AD PubMed:26813123

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

In this work, kinetic analyses revealed that a structural motif in AChE (a hydrophobic sequence of 35 resides peptides) was able to promote amyloid formation and its incorporation into the growing Aβ-fibrils PubMed:26813123

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act(p(HGNC:ACHE)) increases bp(GO:"acetylcholine catabolic process") View Subject | View Object

In addition, several authors observed a reduction in the activity of acetylcholinesterase (AChE), the enzyme that metabolises ACh after its release in the synaptic cleft (Auld et al., 2002; Bowen et al., 1976; Coyle et al., 1983; Davies and Maloney, 1976; Perry et al., 1978) PubMed:25514383

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p(HGNC:ACHE) increases deg(a(CHEBI:acetylcholine)) View Subject | View Object

In most regions that receive cholinergic innervation, the high density of acetylcholinesterase (which can hydrolyze ACh at a rate of one per 100 ms!) might vitiate the volume transmission mechanism PubMed:21482353

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act(p(HGNC:ACHE)) decreases bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Indeed, cholinergic enhancement (via cholinesterase inhibition) reopens the critical period for visual acuity in adult wild-type mice (Morishita et al., 2010), indicating that cellular mechanisms for robust plasticity are maintained in adulthood through the cholinergic system but are suppressed by the action of lynx. PubMed:21482353

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p(HGNC:ACHE) association path(MESH:D058225) View Subject | View Object

In this regard, AChE has been localized to SPs in the vicinity of cholinergic synapses, and experimental evidence suggests that AChE promotes Ab fibrillization [164], suggesting that a further benefit from AChE inhibitor therapy may be to prevent continued Ab deposition in cholinergic projection sites. PubMed:18986241

Appears in Networks:
Annotations
MeSH
Cognitive Dysfunction

p(HGNC:ACHE) increases bp(GO:"GO:1990000") View Subject | View Object

In this regard, AChE has been localized to SPs in the vicinity of cholinergic synapses, and experimental evidence suggests that AChE promotes Ab fibrillization [164], suggesting that a further benefit from AChE inhibitor therapy may be to prevent continued Ab deposition in cholinergic projection sites. PubMed:18986241

Appears in Networks:
Annotations
MeSH
Cognitive Dysfunction

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

A progressive loss of cortical acetylcholinesterase activity has been observed in AD patients with cognitive decline (Shinotoh et al 2000) PubMed:11230871

Appears in Networks:
Annotations
MeSH
Cerebral Cortex

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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.