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p(HGNC:CHAT)

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Entity

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

Appears in Networks 8

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

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

Interplay of neurotransmitters in Alzheimer's disease v1.0.0

M1 muscarinic acetylcholine receptor in Alzheimer’s disease v1.0.0

This file encodes the article M1 muscarinic acetylcholine receptor in Alzheimer’s disease by Jiang et al, 2014

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

Cholinergic system during the progression 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

In-Edges 16

a(MESH:"Cholinergic Neurons") increases act(p(HGNC:CHAT)) View Subject | View Object

Loss of cholinergic neurons has often been demonstrated as lowered ChAT activity in brains of patients with AD. Early post mortem studies indicated a loss of ChAT activity restricted to the neocortex (Slotkin et al., 1990) and this has been confirmed in more recent studies on frontal lobe and temporal cortex (Lai et al., 2006). It is noteworthy that an increase in ChAT activity in the surviving neurons was interpreted as a possible compensatory mechanism (Slotkin et al., 1990). PubMed:19293145

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Annotations
MeSH
Frontal Lobe
MeSH
Neocortex
MeSH
Temporal Lobe

g(HGNC:APOE) negativeCorrelation p(HGNC:CHAT) View Subject | View Object

The APOE-epsilon4 gene-dose effect was also found to correlate with the loss of nAChR binding sites in patients with AD, as well as a reduced respon- siveness to the therapeutic AChE inhibitor tacrine (Poirier et al., 1995). Within an AD cohort, APOE-epsilon4 dose dependently correlates with higher losses of ChAT but not with losses in alpha4beta2 nAChRs (Lai et al., 2006). PubMed:19293145

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

path(MESH:"Alzheimer Disease") decreases act(p(HGNC:CHAT)) 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

Appears in Networks:

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

AD involves loss of cholinergic cells not only in the cortex but also in subcortical nuclei. Up to 50% loss of neurons and of ChAT activity has been reported at autopsy in the locus ceruleus of brains from patients with AD compared with brains from subjects without AD, whereas no change was observed for adrenergic brainstem nuclei (Strong et al., 1991). PubMed:19293145

Appears in Networks:
Annotations
MeSH
Basal Ganglia

bp(GO:"calcium ion import") regulates act(p(HGNC:CHAT)) View Subject | View Object

ChAT activity is regulated by neuronal depolarization, influx of Ca2+ and phosphorylation of the enzyme by a wide variety of protein kinases PubMed:26813123

Appears in Networks:

bp(GO:"membrane depolarization") regulates act(p(HGNC:CHAT)) View Subject | View Object

ChAT activity is regulated by neuronal depolarization, influx of Ca2+ and phosphorylation of the enzyme by a wide variety of protein kinases PubMed:26813123

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:CHAT, pmod(Ph)) regulates act(p(HGNC:CHAT)) View Subject | View Object

ChAT activity is regulated by neuronal depolarization, influx of Ca2+ and phosphorylation of the enzyme by a wide variety of protein kinases PubMed:26813123

Appears in Networks:

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

Moreover, it has been demonstrated that ChAT transcription is severely diminished in the remaining cholinergic neurons, which leads to decreased ChAT activity and progression of dementia PubMed:26813123

Appears in Networks:

path(MESH:"Huntington Disease") negativeCorrelation act(p(HGNC:CHAT)) View Subject | View Object

Moreover, Huntington’s disease appears to be associated with decreased ChAT activity PubMed:26813123

Appears in Networks:

path(MESH:D000544) decreases act(p(HGNC:CHAT), ma(cat)) View Subject | View Object

For example, the activity of choline acetyltransferase, the enzyme that catalyzes the synthesis of ACh from choline and acetyl coenzyme A, is reduced to 35% to 50% of normal levels in Alzheimer's disease PubMed:16273023

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

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

The third important hallmark of AD is cholinergic hypofunction. The neurotransmitter acetylcholine (ACh) exerts its physiological functions by activating either ionotropic nicotinic ACh receptors (nAChRs) or metabotropic muscarinic ACh receptors (mAChRs). It has been reported that in AD brains there are (1) reduced choline acetyltransferase levels accompanied by decreased ACh synthesis; (2) significant loss of cholinergic neurons; (3) reduction in the numbers of postsynaptic neurons accessible to ACh; (4) cholinergic neuronal and axonal abnormalities; and (5) reduction in nAChR levels PubMed:24590577

Appears in Networks:

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

In addition to nAChRs and mAChRs, the enzyme choline acetyltransferase (ChAT), involved in ACh production, is also affected in AD. The activity of this ChAT enzyme, and consequently the synthesis of ACh, is decreased in AD brains PubMed:25514383

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:D000544) decreases p(HGNC:CHAT) 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

Appears in Networks:

path(MESH:D060825) causesNoChange act(p(HGNC:CHAT)) View Subject | View Object

Notably, reports that physostigmine and oral anticholinesterases have beneficial effects for patients with AD suggest that the CBF system is somewhat preserved during the progression of dementia, despite well-documented loss of cholinergic biosynthetic machinery (including ChAT and AChE enzyme deficits) in patients with this disease. Interestingly, recent studies have shown that ChAT activity, which results in acetylcholine (ACh) synthesis, is preserved in the neocortex of people with MCI [18,19]. PubMed:18986241

Appears in Networks:
Annotations
MeSH
Neocortex
MeSH
Cognitive Dysfunction

path(MESH:D060825) increases act(p(HGNC:CHAT)) View Subject | View Object

In fact, our group found elevated ChAT activity in the hippocampus and frontal cortex of subjects with MCI [19,20]. These results suggest that cognitive deficits in MCI and early AD are not associated with a reduction in ChAT activity. Moreover, these data indicate that select components of the hippocampal and cortical cholinergic projection system are capable of compensatory and/ or neuroplasticity responses during the early stages of AD. PubMed:18986241

Appears in Networks:
Annotations
MeSH
Frontal Lobe
MeSH
Hippocampus

path(MESH:D060825) increases act(p(HGNC:CHAT)) View Subject | View Object

In MCI, increased hippocampal and frontal cortex ChAT tone may be important for promoting biochemical activity or compensating for neurodegenerative defects, which may delay the transition of these subjects to frank AD. Hippocampal ChAT activity was increased selectively in MCI cases with high Braak scores (Braak III/IV stage) indicative of advanced disease [19], suggesting that a compensatory upregulation of ChAT may be due, at least in part, to the disconnection of glutamatergic entorhinal cortex input to the hippocampus which occurs early in the disease process [21–23]. In this scenario, upregulation of hippocampal ChAT activity may be due to reactive synaptogenesis, the filling in of denervated glutamatergic synapses by cholinergic input arising from the septum [24]. PubMed:18986241

Appears in Networks:
Annotations
MeSH
Frontal Lobe
MeSH
Hippocampus
MeSH
Cognitive Dysfunction

Out-Edges 12

act(p(HGNC:CHAT)) directlyIncreases rxn(reactants(a(CHEBI:"acetyl-CoA"), a(CHEBI:choline)), products(a(CHEBI:acetylcholine))) View Subject | View Object

From the time of its discovery in 1914 by Henry H. Dale (109) and Otto Loewi (283) (the two shared the Nobel Prize in Physiology and Medicine in 1936) as an agent that decreases heart rate, ACh was recognized as an endogenous signaling compound, synthesized from choline and acetyl-CoA, through the action of choline acetyltransferase, that alters cell function. PubMed:19126755

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:CHAT) negativeCorrelation g(HGNC:APOE) View Subject | View Object

The APOE-epsilon4 gene-dose effect was also found to correlate with the loss of nAChR binding sites in patients with AD, as well as a reduced respon- siveness to the therapeutic AChE inhibitor tacrine (Poirier et al., 1995). Within an AD cohort, APOE-epsilon4 dose dependently correlates with higher losses of ChAT but not with losses in alpha4beta2 nAChRs (Lai et al., 2006). PubMed:19293145

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

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

Appears in Networks:

p(HGNC:CHAT) increases rxn(reactants(a(CHEBI:"acetyl-CoA"), a(CHEBI:choline)), products(a(CHEBI:acetylcholine))) View Subject | View Object

The enzyme choline acetyltransferase (ChAT) can synthesize ACh from choline and acetyl-coenzyme A (acetyl-CoA) PubMed:26813123

Appears in Networks:

act(p(HGNC:CHAT)) negativeCorrelation path(MESH:"Huntington Disease") View Subject | View Object

Moreover, Huntington’s disease appears to be associated with decreased ChAT activity PubMed:26813123

Appears in Networks:

act(p(HGNC:CHAT)) decreases path(MESH:Dementia) View Subject | View Object

Moreover, it has been demonstrated that ChAT transcription is severely diminished in the remaining cholinergic neurons, which leads to decreased ChAT activity and progression of dementia PubMed:26813123

Appears in Networks:

act(p(HGNC:CHAT), ma(cat)) increases a(CHEBI:acetylcholine) View Subject | View Object

For example, the activity of choline acetyltransferase, the enzyme that catalyzes the synthesis of ACh from choline and acetyl coenzyme A, is reduced to 35% to 50% of normal levels in Alzheimer's disease PubMed:16273023

Appears in Networks:

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

The third important hallmark of AD is cholinergic hypofunction. The neurotransmitter acetylcholine (ACh) exerts its physiological functions by activating either ionotropic nicotinic ACh receptors (nAChRs) or metabotropic muscarinic ACh receptors (mAChRs). It has been reported that in AD brains there are (1) reduced choline acetyltransferase levels accompanied by decreased ACh synthesis; (2) significant loss of cholinergic neurons; (3) reduction in the numbers of postsynaptic neurons accessible to ACh; (4) cholinergic neuronal and axonal abnormalities; and (5) reduction in nAChR levels PubMed:24590577

Appears in Networks:

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

In addition to nAChRs and mAChRs, the enzyme choline acetyltransferase (ChAT), involved in ACh production, is also affected in AD. The activity of this ChAT enzyme, and consequently the synthesis of ACh, is decreased in AD brains PubMed:25514383

Appears in Networks:
Annotations
MeSH
Brain

act(p(HGNC:CHAT)) directlyIncreases a(CHEBI:acetylcholine) View Subject | View Object

Notably, reports that physostigmine and oral anticholinesterases have beneficial effects for patients with AD suggest that the CBF system is somewhat preserved during the progression of dementia, despite well-documented loss of cholinergic biosynthetic machinery (including ChAT and AChE enzyme deficits) in patients with this disease. Interestingly, recent studies have shown that ChAT activity, which results in acetylcholine (ACh) synthesis, is preserved in the neocortex of people with MCI [18,19]. PubMed:18986241

Appears in Networks:
Annotations
MeSH
Neocortex
MeSH
Cognitive Dysfunction

act(p(HGNC:CHAT)) decreases bp(HBP:Neurodegeneration) View Subject | View Object

In MCI, increased hippocampal and frontal cortex ChAT tone may be important for promoting biochemical activity or compensating for neurodegenerative defects, which may delay the transition of these subjects to frank AD. Hippocampal ChAT activity was increased selectively in MCI cases with high Braak scores (Braak III/IV stage) indicative of advanced disease [19], suggesting that a compensatory upregulation of ChAT may be due, at least in part, to the disconnection of glutamatergic entorhinal cortex input to the hippocampus which occurs early in the disease process [21–23]. In this scenario, upregulation of hippocampal ChAT activity may be due to reactive synaptogenesis, the filling in of denervated glutamatergic synapses by cholinergic input arising from the septum [24]. PubMed:18986241

Appears in Networks:
Annotations
MeSH
Frontal Lobe
MeSH
Hippocampus
MeSH
Cognitive Dysfunction

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

ACh is produced by the enzyme choline acetyltransferase and its actions are mediated through two types of acetylcholine receptors (AChRs) — the G protein-coupled muscarinic AChRs and the nicotinic AChRs (nAChRs). PubMed:19721446

Appears in Networks:
Annotations
Text Location
Review

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