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PubMed: 26813123

Title
Alzheimer's disease: Targeting the Cholinergic System.
Journal
Current neuropharmacology
Volume
14
Issue
None
Pages
101-15
Date
2016-01-01
Authors
Ribeiro FM | Guimaraes IM | Silva FR | Ferreira-Vieira TH

Evidence 93003ac313
JSON

It has been demonstrated that the cholinergic system plays a role in the learning process

bp(GO:"synaptic transmission, cholinergic") positiveCorrelation bp(GO:learning) View Subject | View Object

Appears in Networks:

bp(GO:learning) positiveCorrelation bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

Evidence 4dd645ba60
JSON

The vesicular transporter activity can be blocked by vesamicol, which is a non-competitive inhibitor

a(CHEBI:"2-(4-phenyl-1-piperidinyl)-1-cyclohexanol") decreases act(p(HGNC:SLC18A3)) View Subject | View Object

Appears in Networks:

a(CHEBI:"2-(4-phenyl-1-piperidinyl)-1-cyclohexanol") decreases tloc(a(CHEBI:acetylcholine), fromLoc(GO:cytosol), toLoc(MESH:"Synaptic Vesicles")) View Subject | View Object

Appears in Networks:

Evidence a1e803c3c5
JSON

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

a(CHEBI:"amyloid-beta") increases a(HBP:"amyloid-beta fibrils") View Subject | View Object

Appears in Networks:

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

Appears in Networks:

Evidence dfeb41dd99
JSON

Interestingly, M1 receptor signaling affects several of AD major hallmarks, including cholinergic deficit, cognitive dysfunction, and tau and Aβ pathologies

act(a(CHEBI:"amyloid-beta")) association act(p(HGNC:CHRM1)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(MESH:"Cholinergic Neurons") association act(p(HGNC:CHRM1)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(p(HGNC:CHRM1)) association a(MESH:"Cholinergic Neurons") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(p(HGNC:CHRM1)) association path(MESH:"Cognitive Dysfunction") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(p(HGNC:CHRM1)) association act(p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(p(HGNC:CHRM1)) association act(a(CHEBI:"amyloid-beta")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(p(HGNC:MAPT)) association act(p(HGNC:CHRM1)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

path(MESH:"Cognitive Dysfunction") association act(p(HGNC:CHRM1)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence fd51b6354c
JSON

However, further studies have demonstrated that nicotinic receptor activation can lead to an increase in Aβ-mediated tau phosphorylation

a(CHEBI:"amyloid-beta") regulates p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(a(MESH:"Receptors, Nicotinic")) increases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 8841584179
JSON

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

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

Appears in Networks:
Annotations
MeSH
Synapses

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

Appears in Networks:
Annotations
MeSH
Synapses

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

Appears in Networks:
Annotations
MeSH
Synapses

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

Appears in Networks:
Annotations
MeSH
Synapses

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

Appears in Networks:
Annotations
MeSH
Synapses

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

Appears in Networks:
Annotations
MeSH
Synapses

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

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

Evidence 94311b1cf2
JSON

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

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

Appears in Networks:

Evidence 21187ec6c6
JSON

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

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

Appears in Networks:

Evidence cca9585c7b
JSON

In a work that evaluated the function of the cholinergic system in mediating the response to stress it was found that treatment of rats with the antagonist of the nicotinic receptor, mecamylamine, attenuates the activation of the HPA axis in response to a stressor agent

a(CHEBI:Mecamylamine) decreases act(a(MESH:"Hypothalamo-Hypophyseal System")) View Subject | View Object

Appears in Networks:

a(MESH:"Receptors, Nicotinic") increases act(a(MESH:"Hypothalamo-Hypophyseal System")) View Subject | View Object

Appears in Networks:

Evidence fe7e2324ae
JSON

Moreover, published data indicate that ACh is involved in memory

a(CHEBI:acetylcholine) positiveCorrelation bp(GO:memory) View Subject | View Object

Appears in Networks:

bp(GO:memory) positiveCorrelation a(CHEBI:acetylcholine) View Subject | View Object

Appears in Networks:

Evidence f0db178e78
JSON

Further studies have demonstrated that endogenous acetylcholine is important for modulation of acquisition [17], encoding [18], consolidation [19], reconsolidation [20], extinction [21] and retrieval of memory

a(CHEBI:acetylcholine) regulates bp(GO:memory) View Subject | View Object

Appears in Networks:

Evidence 41ce3403f7
JSON

It has been demonstrated that the role of ACh in learning and memory seems to be related to the regulation of glutamatergic neurotransmission

a(CHEBI:acetylcholine) association bp(GO:memory) View Subject | View Object

Appears in Networks:

a(CHEBI:acetylcholine) regulates bp(GO:"synaptic transmission, glutamatergic") View Subject | View Object

Appears in Networks:

a(CHEBI:acetylcholine) association bp(GO:learning) View Subject | View Object

Appears in Networks:

bp(GO:learning) association a(CHEBI:acetylcholine) View Subject | View Object

Appears in Networks:

bp(GO:memory) association a(CHEBI:acetylcholine) View Subject | View Object

Appears in Networks:

Evidence 51b6cdd894
JSON

Stress is another factor that can regulate ACh release in the forebrain and its function on the hypothalamic-pituitaryadrenal (HPA) system can modulate biological and emotional outcomes

a(CHEBI:acetylcholine) regulates a(MESH:"Hypothalamo-Hypophyseal System") View Subject | View Object

Appears in Networks:

bp(GO:"response to stress") regulates tloc(a(CHEBI:acetylcholine), fromLoc(GO:intracellular), toLoc(MESH:"Basal Forebrain")) View Subject | View Object

Appears in Networks:

Evidence cb66d96f58
JSON

Similarly, nicotine can mimic the ACh effects on the HPA axis by activating nicotinic receptors

a(CHEBI:acetylcholine) increases act(a(MESH:"Receptors, Nicotinic")) View Subject | View Object

Appears in Networks:

a(CHEBI:nicotine) increases act(a(MESH:"Receptors, Nicotinic")) View Subject | View Object

Appears in Networks:

Evidence d2bcedf4f7
JSON

ACh contributes to auditory synaptic transmission by facilitating thalamocortical communication

a(CHEBI:acetylcholine) increases bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

Evidence 47ff181576
JSON

Recent evidences also suggest the involvement of ACh in adult neurogenesis

a(CHEBI:acetylcholine) increases bp(GO:neurogenesis) View Subject | View Object

Appears in Networks:

Evidence baf5009870
JSON

When cholinergic neurons are depolarized, ACh is exocytosed from synaptic vesicles and released into the synaptic cleft, where it can activate both muscarinic and nicotinic receptors

a(CHEBI:acetylcholine) increases act(p(FPLX:CHRM)) View Subject | View Object

Appears in Networks:

a(CHEBI:acetylcholine) increases act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

bp(GO:"membrane depolarization") increases tloc(a(CHEBI:acetylcholine), fromLoc(MESH:"Synaptic Vesicles"), toLoc(GO:"synaptic cleft")) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
cholinergic neuron

Evidence 7c9aac530e
JSON

Choline that is released by ACh hydrolysis in the synaptic cleft is continuously reuptaken into the presynaptic cholinergic neuron by an active transport system (see Fig. 1)

deg(a(CHEBI:acetylcholine)) increases a(CHEBI:choline) View Subject | View Object

Appears in Networks:

p(HGNC:SLC5A7) increases tloc(a(CHEBI:choline), fromLoc(GO:"synaptic cleft"), toLoc(MESH:"Cholinergic Neurons")) View Subject | View Object

Appears in Networks:

Evidence bbb61a5b86
JSON

Thus, ACh can influence the strength and fidelity of various synapses and modulate overall CNS neurotransmission

a(CHEBI:acetylcholine) regulates bp(MESH:"Synaptic Transmission") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Central Nervous System

Evidence 8b0c6f75a1
JSON

Because ACh has an important role in cognitive processes, the cholinergic system is pointed as an important factor in many forms of dementia, including AD

a(CHEBI:acetylcholine) association bp(GO:cognition) View Subject | View Object

Appears in Networks:

bp(GO:"synaptic transmission, cholinergic") association path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

bp(GO:"synaptic transmission, cholinergic") association path(MESH:Dementia) View Subject | View Object

Appears in Networks:

bp(GO:cognition) association a(CHEBI:acetylcholine) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

path(MESH:Dementia) association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

Evidence 9d67016fd4
JSON

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

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

Appears in Networks:

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

Appears in Networks:

Evidence ac350fd9a9
JSON

The two best known muscarinic receptor antagonists are atropine and quinuclidinyl benzilate, which block all muscarinic receptors

a(CHEBI:atropine) decreases act(p(FPLX:CHRM)) View Subject | View Object

Appears in Networks:

a(MESH:"Quinuclidinyl Benzilate") decreases act(p(FPLX:CHRM)) View Subject | View Object

Appears in Networks:

Evidence 41c8923cd8
JSON

CHT1 is mainly found in cholinergic neurons [92-94] and is responsible for supplying choline for the synthesis of ACh

a(CHEBI:choline) increases a(CHEBI:acetylcholine) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
cholinergic neuron

p(HGNC:SLC5A7) increases a(CHEBI:choline) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
cholinergic neuron

Evidence 01b5979808
JSON

It has been demonstrated that treatment with donepezil is associated with significant cognitive and functional benefits over the course of 12 months in patients with moderate to severe AD

a(CHEBI:donepezil) increases bp(GO:cognition) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 3cbadd5703
JSON

In a double-blind study designed to assess patients survival with mild to moderately severe AD, the long-term treatment (2 years) with galantamine significantly reduced mortality and cognition decline, besides improving daily live activities in mild to moderate AD patients

a(CHEBI:galanthamine) decreases path(MESH:Death) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:galanthamine) increases bp(GO:cognition) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence ba7d2924b7
JSON

In fact, memantine is able to reduce the excitotoxicity in AD

a(CHEBI:memantine) decreases a(HBP:Excitotoxicity) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence fd96a51a83
JSON

Rivastigmine has also been used for AD treatment due to its ease of use (transdermal patch) and good tolerability by patients

a(CHEBI:rivastigmine) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

path(MESH:"Alzheimer Disease") negativeCorrelation a(CHEBI:rivastigmine) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 02bf012cbe
JSON

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

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

Appears in Networks:

Evidence dcf81e32c6
JSON

Curare is the best known antagonist for nicotinic receptors, although this drug is not capable of blocking central nicotinic receptors

a(CHEBI:tubocurarine) decreases act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

Evidence 590c1573d1
JSON

In a large-scale placebo-controlled clinical trial, it was demonstrated that xanomeline, a muscarinic agonist with reasonable selectivity for M1/M4 receptors, exhibits a positive effect in minimizing, in a dose-dependent manner, cognitive and psychiatric symptoms in AD, including memory deficit, mood disturbance, agitation and hallucinations

a(CHEBI:xanomeline) increases bp(GO:cognition) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:xanomeline) increases bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:xanomeline) decreases path(MESH:"Mood Disorders") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:xanomeline) decreases path(MESH:"Psychomotor Agitation") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:xanomeline) decreases path(MESH:Hallucinations) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence c0d1a30e56
JSON

It has been demonstrated that cholinergic synapses are particularly affected by Aβ oligomers early neurotoxicity [218, 219] and that synaptic loss is the major correlate of cognitive impairment

act(a(GO:"cholinergic synapse")) association a(HBP:"amyloid-beta oligomers") View Subject | View Object

Appears in Networks:

a(GO:synapse) negativeCorrelation path(MESH:"Cognitive Dysfunction") View Subject | View Object

Appears in Networks:

a(HBP:"amyloid-beta oligomers") association act(a(GO:"cholinergic synapse")) View Subject | View Object

Appears in Networks:

path(MESH:"Cognitive Dysfunction") negativeCorrelation a(GO:synapse) View Subject | View Object

Appears in Networks:

Evidence 26ced0577e
JSON

Moreover, AF267B treatment leads to an increase in alpha secretase, which is an enzyme that can prevent the production of Aβ peptide

a(MESH:"Amyloid Precursor Protein Secretases") decreases a(MESH:"Amyloid beta-Peptides") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:10013505) increases a(MESH:"Amyloid Precursor Protein Secretases") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 6a700bc9aa
JSON

The loss of the nucleus basalis cholinergic neurons in AD patients is severe: from about 500,000 in the healthy adult to less than 100,000 in patients displaying advanced AD

a(MESH:"Basal Nucleus of Meynert") negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") negativeCorrelation a(MESH:"Basal Nucleus of Meynert") View Subject | View Object

Appears in Networks:

Evidence 8cb2e40b36
JSON

Experimental data using non-human primates and rodents have demonstrated that injuries introduced to basal forebrain cholinergic neurons that innervate the cortex lead to attention deficit

act(a(MESH:"Cholinergic Neurons")) increases path(MESH:Attention) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Basal Forebrain

Evidence cc4f9a8935
JSON

All these cholinergic alterations that take place in AD closely correlates with impaired attention and memory observed in patients

a(MESH:"Cholinergic Neurons") increases path(MESH:Attention) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(MESH:"Cholinergic Neurons") increases bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 893679814f
JSON

The importance of the cholinergic neurons from the nucleus basalis of Meynert on memory is highlighted by the fact that the specific degeneration of these neurons takes place in Alzheimer’s disease (AD) and contributes to the memory loss exhibited by AD patients

a(MESH:"Cholinergic Neurons") positiveCorrelation bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Basal Nucleus of Meynert

bp(GO:memory) positiveCorrelation a(MESH:"Cholinergic Neurons") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Basal Nucleus of Meynert

bp(GO:memory) negativeCorrelation bp(HBP:Neurodegeneration) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

bp(HBP:Neurodegeneration) negativeCorrelation bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence d2cca42c7e
JSON

It has been demonstrated that stimulation of cholinergic neurons in precise regions of the brainstem can promote REM (rapid eye movement) sleep, dose-dependently

a(MESH:"Cholinergic Neurons") increases bp(GO:"circadian sleep/wake cycle, REM sleep") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain Stem

Evidence 4b7391e234
JSON

ACh synthesis takes place in the cytoplasm of cholinergic neurons

a(MESH:"Cholinergic Neurons") increases a(CHEBI:acetylcholine) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cytoplasm

Evidence 8ae5655a83
JSON

Although cholinergic neurons can synthesize choline, the de novo synthesis contributes only with a very small fraction of the total choline that is needed for ACh synthesis (see Fig. 1)

a(MESH:"Cholinergic Neurons") increases a(CHEBI:choline) View Subject | View Object

Appears in Networks:

Evidence f3b12ba676
JSON

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

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

Appears in Networks:

Evidence f31a4979d7
JSON

It has been postulated that the loss of cholinergic neurons and the consequent impairment in dopaminergic transmission could be the main factors underling AD-related psychiatric symptoms

a(MESH:"Cholinergic Neurons") increases bp(GO:"synaptic transmission, dopaminergic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA3 Region, Hippocampal

a(MESH:"Cholinergic Neurons") decreases path(MESH:Apathy) View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA3 Region, Hippocampal
MeSH
Alzheimer Disease

a(MESH:"Cholinergic Neurons") decreases path(MESH:Depression) View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA3 Region, Hippocampal
MeSH
Alzheimer Disease

Evidence ef25aba336
JSON

Further highlighting the importance of the cholinergic system in the CNS, cholinergic neuronal loss, especially in the basal forebrain, occurs not only in AD, but also in Parkinson’s disease [190, 191], Down syndrome [192], amyotrophic lateral sclerosis [193, 194], progressive supranuclear palsy [195, 196], and olivopontocerebellar atrophy [197]

a(MESH:"Cholinergic Neurons") negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Basal Forebrain
MeSH
Central Nervous System

a(MESH:"Cholinergic Neurons") negativeCorrelation path(MESH:"Parkinson Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Basal Forebrain
MeSH
Central Nervous System

a(MESH:"Cholinergic Neurons") negativeCorrelation path(MESH:"Down Syndrome") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Basal Forebrain
MeSH
Central Nervous System

a(MESH:"Cholinergic Neurons") negativeCorrelation path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Basal Forebrain
MeSH
Central Nervous System

a(MESH:"Cholinergic Neurons") negativeCorrelation path(MESH:"Supranuclear Palsy, Progressive") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Basal Forebrain
MeSH
Central Nervous System

a(MESH:"Cholinergic Neurons") negativeCorrelation path(MESH:"Olivopontocerebellar Atrophies") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Basal Forebrain
MeSH
Central Nervous System

path(MESH:"Alzheimer Disease") negativeCorrelation a(MESH:"Cholinergic Neurons") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Basal Forebrain
MeSH
Central Nervous System

path(MESH:"Amyotrophic Lateral Sclerosis") negativeCorrelation a(MESH:"Cholinergic Neurons") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Basal Forebrain
MeSH
Central Nervous System

path(MESH:"Down Syndrome") negativeCorrelation a(MESH:"Cholinergic Neurons") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Basal Forebrain
MeSH
Central Nervous System

path(MESH:"Olivopontocerebellar Atrophies") negativeCorrelation a(MESH:"Cholinergic Neurons") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Basal Forebrain
MeSH
Central Nervous System

path(MESH:"Parkinson Disease") negativeCorrelation a(MESH:"Cholinergic Neurons") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Basal Forebrain
MeSH
Central Nervous System

path(MESH:"Supranuclear Palsy, Progressive") negativeCorrelation a(MESH:"Cholinergic Neurons") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Basal Forebrain
MeSH
Central Nervous System

Evidence cb34434332
JSON

Cholinesterase inhibitors can increase ACh levels in the synaptic cleft and partially ameliorate cognitive symptoms, enhance quality of life and diminish caregiver burden for patients with mild to severe AD

a(MESH:"Cholinesterase Inhibitors") increases a(CHEBI:acetylcholine) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(MESH:"Cholinesterase Inhibitors") increases bp(GO:cognition) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 28e36bfe97
JSON

Furthermore, it has also been proposed that the nerve growth factor (NGF) has the potential to preserve cholinergic neurons

a(MESH:"Nerve Growth Factor") increases a(MESH:"Cholinergic Neurons") View Subject | View Object

Appears in Networks:

Evidence 5327cb1292
JSON

Moreover, previous studies have shown that treatment with NGF can counteract cholinergic atrophy and memory deficits in aged rats

a(MESH:"Nerve Growth Factor") increases a(MESH:"Cholinergic Neurons") View Subject | View Object

Appears in Networks:

a(MESH:"Nerve Growth Factor") increases bp(GO:memory) View Subject | View Object

Appears in Networks:

Evidence c3aca28e57
JSON

It has been demonstrated that phosphorylation of nicotinic receptors by protein kinase A, protein kinase C, and tyrosine kinase can regulate receptor activity

a(MESH:"Protein-Tyrosine Kinases") increases p(FPLX:CHRN, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(FPLX:CHRN, pmod(Ph)) regulates act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

p(FPLX:PKA) increases p(FPLX:CHRN, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(FPLX:PKC) increases p(FPLX:CHRN, pmod(Ph)) View Subject | View Object

Appears in Networks:

Evidence 155f8f6c3e
JSON

Moreover, it has been shown that blocking CA3 cholinergic receptors impairs the encoding of information and memory

a(MESH:"Receptors, Cholinergic") increases bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA3 Region, Hippocampal

Evidence 9c5a55359b
JSON

In the peripheral nervous system, activation of nicotinic receptors leads to rapid synaptic transmission

act(a(MESH:"Receptors, Nicotinic")) increases bp(MESH:"Synaptic Transmission") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Peripheral Nervous System

Evidence 502ed65673
JSON

In the CNS, most of the nicotinic receptors are expressed at the presynaptic neuronal membrane and their main role is to regulate the release of neurotransmitters, whereas nicotinic receptors expressed in the peripheral nervous system are mainly post-synaptic

a(MESH:"Receptors, Nicotinic") regulates tloc(a(CHEBI:neurotransmitter), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

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

Evidence 6a90aea776
JSON

Moreover, the M1 agonist AF267B can rescue the cognitive impairment and decrease Aβ42 and tau abnormalities in the cortex and hippocampus of a mouse model of AD

a(PUBCHEM:10013505) increases act(p(HGNC:CHRM1)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Neocortex
MeSH
Alzheimer Disease

a(PUBCHEM:10013505) increases bp(GO:cognition) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Neocortex
MeSH
Alzheimer Disease

a(PUBCHEM:10013505) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Neocortex
MeSH
Alzheimer Disease

a(PUBCHEM:10013505) decreases p(HGNC:MAPT, var("?")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Neocortex
MeSH
Alzheimer Disease

Evidence d92c148973
JSON

For example, it has been shown that the benzyl quinolone carboxylic acid (BQCA), which is an M1-selective allosteric agonist, is effective in increasing spontaneous excitatory postsynaptic currents in the medial prefrontal cortex (mPFC) pyramidal cells and improving memory in a transgenic mouse model of AD

a(PUBCHEM:1476756) increases bp(GO:"excitatory postsynaptic potential") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Pyramidal Cells
MeSH
Alzheimer Disease

a(PUBCHEM:1476756) increases bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Pyramidal Cells
MeSH
Alzheimer Disease

Evidence faee482c10
JSON

Moreover, the use of M2 antagonists, such as SCH-57790 and SC-72788, can lead to blockage of M2-mediated inhibition of presynaptic release of ACh, which can activate M1 and nicotinic receptors, ameliorating cognitive impairment in AD

a(PUBCHEM:9867750) increases tloc(a(CHEBI:acetylcholine), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:9867750) increases act(p(HGNC:CHRM1)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:9867750) increases act(a(MESH:"Receptors, Nicotinic")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:9867750) increases bp(GO:cognition) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:CHRM2) decreases tloc(a(CHEBI:acetylcholine), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 1b8c808ca5
JSON

Interestingly, it has been demonstrated that an increase in neuronal firing can lead to an increase in choline uptake and in the synthesis of ACh

bp(GO:"action potential initiation") increases tloc(a(CHEBI:choline), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Appears in Networks:

bp(GO:"action potential initiation") increases a(CHEBI:acetylcholine) View Subject | View Object

Appears in Networks:

Evidence 6632504a7f
JSON

It is possible that the presence of CHT1 in the membrane of synaptic vesicles and the consequent increase in CHT1 relocation to the plasma membrane following neuronal depolarization could explain why an increase in neuronal firing promotes increased choline reuptake and, thus, ACh synthesis

bp(GO:"action potential initiation") increases tloc(a(CHEBI:choline), fromLoc(GO:"synaptic cleft"), toLoc(MESH:"Cholinergic Neurons")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Membranes
MeSH
Synaptic Vesicles

bp(GO:"action potential initiation") increases a(CHEBI:acetylcholine) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Membranes
MeSH
Synaptic Vesicles

bp(GO:"action potential initiation") association complex(a(GO:"plasma membrane"), p(HGNC:SLC5A7)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

bp(GO:"membrane depolarization") increases complex(a(GO:"plasma membrane"), p(HGNC:SLC5A7)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

complex(a(GO:"plasma membrane"), p(HGNC:SLC5A7)) association bp(GO:"action potential initiation") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:SLC5A7) increases tloc(a(CHEBI:choline), fromLoc(GO:"synaptic cleft"), toLoc(MESH:"Cholinergic Neurons")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Membranes
MeSH
Synaptic Vesicles

p(HGNC:SLC5A7) increases a(CHEBI:acetylcholine) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Membranes
MeSH
Synaptic Vesicles

Evidence 80566c3dbd
JSON

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

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

Appears in Networks:

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

Appears in Networks:
Annotations
MeSH
Neurons

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

Appears in Networks:

Evidence 551785ea37
JSON

The cholinergic system is involved in critical physiological processes, such as attention, learning, memory, stress response, wakefulness and sleep, and sensory information

bp(GO:"regulation of circadian sleep/wake cycle, sleep") association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

bp(GO:"regulation of circadian sleep/wake cycle, wakefulness") association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

bp(GO:"response to stress") association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

bp(GO:"sensory processing") association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

bp(GO:"synaptic transmission, cholinergic") association path(MESH:Attention) View Subject | View Object

Appears in Networks:

bp(GO:"synaptic transmission, cholinergic") association bp(GO:learning) View Subject | View Object

Appears in Networks:

bp(GO:"synaptic transmission, cholinergic") association bp(GO:memory) View Subject | View Object

Appears in Networks:

bp(GO:"synaptic transmission, cholinergic") association bp(GO:"response to stress") View Subject | View Object

Appears in Networks:

bp(GO:"synaptic transmission, cholinergic") association bp(GO:"regulation of circadian sleep/wake cycle, wakefulness") View Subject | View Object

Appears in Networks:

bp(GO:"synaptic transmission, cholinergic") association bp(GO:"regulation of circadian sleep/wake cycle, sleep") View Subject | View Object

Appears in Networks:

bp(GO:"synaptic transmission, cholinergic") association bp(GO:"sensory processing") View Subject | View Object

Appears in Networks:

bp(GO:learning) association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

bp(GO:memory) association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

path(MESH:Attention) association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

Evidence fd147f590b
JSON

Given its widespread distribution in the brain, it is not surprising that cholinergic neurotransmission is responsible for modulating important neural functions

bp(GO:"synaptic transmission, cholinergic") regulates act(a(MESH:Neurons)) View Subject | View Object

Appears in Networks:

Evidence 48942b114e
JSON

On the other hand, the facilitation of the cholinergic transmission by using the cholinesterase inhibitors can improve attention in humans

bp(GO:"synaptic transmission, cholinergic") increases path(MESH:Attention) View Subject | View Object

Appears in Networks:

Evidence f021bed41a
JSON

Disruption of cholinergic inputs to the cortex can impair attention and the use of instructive cues needed for decision-making related to ongoing behavior

bp(GO:"synaptic transmission, cholinergic") increases path(MESH:Attention) View Subject | View Object

Appears in Networks:

Evidence 40ad80c169
JSON

Another important function of the cholinergic system is to regulate the sleep cycle

bp(GO:"synaptic transmission, cholinergic") regulates bp(GO:"circadian sleep/wake cycle") View Subject | View Object

Appears in Networks:

Evidence 17024ea322
JSON

Moreover, the interaction of the cholinergic and glutamatergic systems seems to be important not only for cognitive processes but also for neuroprotection, as it has been shown that nicotinic receptors agonists are neuroprotective in a mechanism that is Ca2+-dependent and that involves the glutamatergic system

bp(GO:"synaptic transmission, cholinergic") association bp(GO:cognition) View Subject | View Object

Appears in Networks:

bp(GO:"synaptic transmission, cholinergic") association bp(HBP:Neurodegeneration) View Subject | View Object

Appears in Networks:

bp(GO:"synaptic transmission, glutamatergic") association bp(GO:cognition) View Subject | View Object

Appears in Networks:

bp(GO:"synaptic transmission, glutamatergic") association bp(HBP:Neurodegeneration) View Subject | View Object

Appears in Networks:

bp(GO:cognition) association bp(GO:"synaptic transmission, glutamatergic") View Subject | View Object

Appears in Networks:

bp(GO:cognition) association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

bp(HBP:Neurodegeneration) association bp(GO:"synaptic transmission, glutamatergic") View Subject | View Object

Appears in Networks:

bp(HBP:Neurodegeneration) association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Appears in Networks:

p(FPLX:CHRN) decreases bp(HBP:Neurodegeneration) View Subject | View Object

Appears in Networks:

Evidence f14eb7f656
JSON

In fact, the memory deficit and neuropathology severity observed in patients exhibiting AD highly correlate with changes in hippocampal synaptic transmission, especially with changes in synaptophysin expression, a presynaptic vesicle protein

bp(GO:memory) association bp(MESH:"Synaptic Transmission") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

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

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

bp(MESH:"Synaptic Transmission") association bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

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

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

Evidence 30953e1891
JSON

Not only nicotine, but also DMPP (1,1-Dimethyl-4- phenylpiperazinium) and cystine can act as nicotinic receptor agonists

complex(a(CHEBI:"1,1-dimethyl-4-phenylpiperazinium iodide"), p(FPLX:CHRN)) increases act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

complex(a(CHEBI:cystine), p(FPLX:CHRN)) increases act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

complex(a(CHEBI:nicotine), p(FPLX:CHRN)) increases act(p(FPLX:CHRN)) View Subject | View Object

Appears in Networks:

Evidence e8607ecc93
JSON

Agonists of nicotinic ACh receptors can improve, while antagonists for the receptor impair, performance in cognitive tasks

p(FPLX:CHRN) increases bp(GO:cognition) View Subject | View Object

Appears in Networks:

Evidence 654c367bb5
JSON

The first selective agonist identified for muscarinic receptors was muscarine and, so far, there is no agonist available with a specific selectivity for one particular subtype of muscarinic receptor

complex(a(CHEBI:Muscarine), p(FPLX:CHRM)) increases act(p(FPLX:CHRM)) View Subject | View Object

Appears in Networks:

Evidence 217d8e630d
JSON

Muscarinic receptors are G protein coupled receptors that are capable of modulating a wide variety of ion channels

p(FPLX:CHRM) regulates a(MESH:"Ion Channels") View Subject | View Object

Appears in Networks:

Evidence bba3e21c46
JSON

As a consequence, stimulation of ACh muscarinic receptors can promote the opening or closing of Ca2+, K+, or Cl- channels, which might facilitate either depolarization or hyperpolarization, depending on the cell type where these receptors are expressed

p(FPLX:CHRM) regulates act(a(MESH:"Calcium Channels")) View Subject | View Object

Appears in Networks:

p(FPLX:CHRM) regulates act(a(MESH:"Potassium Channels")) View Subject | View Object

Appears in Networks:

p(FPLX:CHRM) regulates act(a(MESH:"Chloride Channels")) View Subject | View Object

Appears in Networks:

Evidence a97b76f7ea
JSON

Activation of muscarinic receptors can block various types of K+ currents by inhibiting many resting and voltage-gated K+ channels

act(p(FPLX:CHRM)) decreases act(a(MESH:"Potassium Channels")) View Subject | View Object

Appears in Networks:

Evidence f0838b7728
JSON

In addition to decreasing K+ currents, muscarinic receptors located at the presynaptic region can also inhibit GABAergic neurotransmission

act(p(FPLX:CHRM)) decreases bp(GO:"synaptic transmission, glutamatergic") View Subject | View Object

Appears in Networks:

Evidence c7141a53e3
JSON

Two choline transporters have been identified in neurons: a ubiquitous, low-affinity, sodium-independent transporter that can only be inhibited by high concentrations of hemicholinium-3 (HC-3) (Ki of about 50 μM), and a highaffinity, sodium-dependent, HC-3-sensitive (Ki of 10-100 nM) choline transporter (CHT1)

p(HGNC:SLC5A7) increases tloc(a(CHEBI:choline), fromLoc(GO:"synaptic cleft"), toLoc(MESH:"Cholinergic Neurons")) View Subject | View Object

Appears in Networks:

Evidence 82f06c0a27
JSON

A molecular modeling study showed that AChE interacts with the Aβ peptide and promotes amyloid fibril formation

complex(a(MESH:"Amyloid beta-Peptides"), p(HGNC:ACHE)) increases a(HBP:"amyloid-beta fibrils") View Subject | View Object

Appears in Networks:

Evidence 3e2b9a8d6e
JSON

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

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

Appears in Networks:

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

Appears in Networks:

Evidence ca177c20e3
JSON

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

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

Appears in Networks:

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

Appears in Networks:

Evidence f10c5a7704
JSON

In fact, it has been shown that APP interacts with CHT1 proteins increasing their endocytosis from the cell surface [258] and that mice that display disruption of CHT1 gene expression exhibit symptoms related to ACh deficit

complex(p(HGNC:APP), p(HGNC:SLC5A7)) increases tloc(p(HGNC:APP), fromLoc(GO:"cell surface"), toLoc(GO:intracellular)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 01d2ccb1cb
JSON

Stimulation of Gαq coupled muscarinic receptors leads to activation of phospholipase C and formation of inositol phosphates and other second messengers, which can promote closure of K+ channels, thus facilitating cell excitability

complex(p(HGNC:CHRM1), p(INTERPRO:"G-protein alpha subunit, group Q")) increases act(p(FPLX:PLC)) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRM1), p(INTERPRO:"G-protein alpha subunit, group Q")) increases a(CHEBI:"myo-inositol") View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRM1), p(INTERPRO:"G-protein alpha subunit, group Q")) decreases act(a(MESH:"Potassium Channels")) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRM3), p(INTERPRO:"G-protein alpha subunit, group Q")) increases act(p(FPLX:PLC)) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRM3), p(INTERPRO:"G-protein alpha subunit, group Q")) increases a(CHEBI:"myo-inositol") View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRM3), p(INTERPRO:"G-protein alpha subunit, group Q")) decreases act(a(MESH:"Potassium Channels")) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRM5), p(INTERPRO:"G-protein alpha subunit, group Q")) increases act(p(FPLX:PLC)) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRM5), p(INTERPRO:"G-protein alpha subunit, group Q")) increases a(CHEBI:"myo-inositol") View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRM5), p(INTERPRO:"G-protein alpha subunit, group Q")) decreases act(a(MESH:"Potassium Channels")) View Subject | View Object

Appears in Networks:

Evidence c8744d3dff
JSON

On the other hand, stimulation of Gαq coupled muscarinic receptors generates intracellular second messengers that can facilitate N-methyl-D-aspartate (NMDA) currents

complex(p(HGNC:CHRM1), p(INTERPRO:"G-protein alpha subunit, group Q")) increases a(MESH:"Receptors, N-Methyl-D-Aspartate") View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRM3), p(INTERPRO:"G-protein alpha subunit, group Q")) increases a(MESH:"Receptors, N-Methyl-D-Aspartate") View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRM5), p(INTERPRO:"G-protein alpha subunit, group Q")) increases a(MESH:"Receptors, N-Methyl-D-Aspartate") View Subject | View Object

Appears in Networks:

Evidence 424e9c9901
JSON

It has been demonstrated that M1 muscarinic receptors coupling to G-proteins is impaired in the neocortex of AD patients and that the extent of M1/G-protein uncoupling is related to the severity of cognitive symptoms in AD

complex(p(HGNC:CHRM1), p(INTERPRO:"G-protein alpha subunit, group Q")) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neocortex
MeSH
Alzheimer Disease

complex(p(HGNC:CHRM1), p(INTERPRO:"G-protein alpha subunit, group Q")) increases bp(GO:cognition) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neocortex
MeSH
Alzheimer Disease

path(MESH:"Alzheimer Disease") negativeCorrelation complex(p(HGNC:CHRM1), p(INTERPRO:"G-protein alpha subunit, group Q")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neocortex
MeSH
Alzheimer Disease

Evidence 28e68fd5a4
JSON

It has been shown that activation of M1 receptors decreases tau hyperphosphorylation via activation of PKC and inhibition of GSK-3β

act(p(HGNC:CHRM1)) decreases p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(p(HGNC:CHRM1)) increases act(p(FPLX:PKC)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(p(HGNC:CHRM1)) decreases act(p(HGNC:GSK3B)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 70ef8a87b6
JSON

Activation of Gαi coupled muscarinic receptors leads to inhibition of adenylyl cyclase and reduction of cyclic adenosine monophosphate (cAMP) levels, promoting inhibition of voltage-gated Ca2+ channels and, thus, diminishing cell excitability

complex(p(HGNC:CHRM2), p(INTERPRO:"G-protein alpha subunit, group I")) decreases p(FPLX:ADCY) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRM2), p(INTERPRO:"G-protein alpha subunit, group I")) decreases a(CHEBI:"3',5'-cyclic AMP") View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRM4), p(INTERPRO:"G-protein alpha subunit, group I")) decreases p(FPLX:ADCY) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRM2), p(INTERPRO:"G-protein alpha subunit, group I")) decreases act(a(MESH:"Calcium Channels")) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRM4), p(INTERPRO:"G-protein alpha subunit, group I")) decreases a(CHEBI:"3',5'-cyclic AMP") View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRM4), p(INTERPRO:"G-protein alpha subunit, group I")) decreases act(a(MESH:"Calcium Channels")) View Subject | View Object

Appears in Networks:

Evidence c273a2ec45
JSON

In addition, activation of M2 receptors can cause an increase in Aβ production

act(p(HGNC:CHRM2)) increases a(CHEBI:"amyloid-beta") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 29bbddbd30
JSON

Cholinergic nicotinic receptors expressed in muscle and ganglia are comprised of two α subunits plus each of the other three

complex(p(HGNC:CHRNA1), p(HGNC:CHRNA1), p(HGNC:CHRNB1), p(HGNC:CHRND), p(HGNC:CHRNG)) increases p(FPLX:CHRN) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Ganglia
MeSH
Muscles

Evidence 831aae331e
JSON

Nicotinic receptors are formed by five different subunits: α, β, δ, and γ (fetal) or ε (adult)

p(HGNC:CHRNB1) increases a(MESH:"Receptors, Nicotinic") View Subject | View Object

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

p(HGNC:CHRNA1) increases a(MESH:"Receptors, Nicotinic") View Subject | View Object

Appears in Networks:

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

Appears in Networks:

Evidence cfcfe59001
JSON

Interestingly, PKC can phosphorylate VAChT and regulate its vesicular localization

p(FPLX:PKC) increases p(HGNC:SLC18A3, pmod(Ph)) View Subject | View Object

Appears in Networks:

Evidence cc118aa37b
JSON

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

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

Appears in Networks:

Evidence b6512ea2ed
JSON

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

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

Appears in Networks:

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

Appears in Networks:

Evidence 5b07e952f6
JSON

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

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

Appears in Networks:

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

Appears in Networks:

Evidence cc7ab4c613
JSON

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

p(HGNC:CHRNA10) increases a(MESH:"Receptors, Nicotinic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:CHRNA2) increases a(MESH:"Receptors, Nicotinic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:CHRNA3) increases a(MESH:"Receptors, Nicotinic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:CHRNA4) increases a(MESH:"Receptors, Nicotinic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:CHRNA5) increases a(MESH:"Receptors, Nicotinic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:CHRNA6) increases a(MESH:"Receptors, Nicotinic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

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

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:CHRNA9) increases a(MESH:"Receptors, Nicotinic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:CHRNB2) increases a(MESH:"Receptors, Nicotinic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:CHRNB3) increases a(MESH:"Receptors, Nicotinic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:CHRNB4) increases a(MESH:"Receptors, Nicotinic") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

Evidence 4bda05da79
JSON

Following that, the neurotransmitter is transported by the vesicular acetylcholine transporter (VAChT) from the cytosol into synaptic vesicles

p(HGNC:SLC18A3) increases tloc(a(CHEBI:acetylcholine), fromLoc(GO:cytosol), toLoc(MESH:"Synaptic Vesicles")) View Subject | View Object

Appears in Networks:

Evidence 3285df1e44
JSON

Each molecule of ACh transported by VAChT is in exchange for two vesicular protons, which leads to the fulfill of synaptic vesicles with the neurotransmitter

p(HGNC:SLC18A3) increases tloc(a(CHEBI:acetylcholine), fromLoc(GO:cytosol), toLoc(MESH:"Synaptic Vesicles")) View Subject | View Object

Appears in Networks:

p(HGNC:SLC18A3) increases tloc(a(CHEBI:proton), fromLoc(MESH:"Synaptic Vesicles"), toLoc(GO:cytosol)) View Subject | View Object

Appears in Networks:

Evidence 6483f3a58c
JSON

In addition, quantitative autoradiography assay revealed that choline uptake was reduced in the hippocampus of these animals and that the expression of muscarinic and nicotinic cholinergic receptors was diminished

p(MGI:App, var("?")) decreases tloc(a(CHEBI:choline), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus

p(MGI:App, var("?")) decreases p(FPLX:CHRM) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus

p(MGI:App, var("?")) decreases p(FPLX:CHRN) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hippocampus

Evidence a016ee2973
JSON

Corroborating this hypothesis, it has been demonstrated that dopamine efflux is increased in the nucleus accumbens of M4 knockout mice

p(MGI:Chrm4) decreases tloc(a(CHEBI:dopamine), fromLoc(GO:intracellular), toLoc(GO:"extracellular region")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA3 Region, Hippocampal

Evidence dc779961e8
JSON

A VAChT knockdown mouse model, expressing about 68% less VAChT protein, shows major neuromuscular deficits

p(MGI:Slc18a3) decreases path(MESH:"Neuromuscular Diseases") View Subject | View Object

Appears in Networks:

Evidence 24779e4ae0
JSON

Furthermore, cognitive impairment can take place even due to a mild decrease in VAChT protein expression (about 45%)

p(MGI:Slc18a3) increases bp(GO:cognition) View Subject | View Object

Appears in Networks:

Evidence eedc42239e
JSON

Moreover, mice that display a disruption of CHT1 gene expression exhibit symptoms related to ACh deficit and inevitable death within an hour of birth

p(MGI:Slc5a7) decreases path(MESH:Death) View Subject | View Object

Appears in Networks:

Evidence ff46207bc0
JSON

Importantly, the neurons that form the nucleus basalis of Meynert undergo extensive degeneration in AD

path(MESH:"Alzheimer Disease") increases deg(a(MESH:"Basal Nucleus of Meynert")) View Subject | View Object

Appears in Networks:

Evidence ac1c92853e
JSON

In addition to cognitive alterations, psychiatric symptoms are frequently observed in AD patients, including apathy and depression

path(MESH:"Alzheimer Disease") positiveCorrelation path(MESH:Apathy) View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA3 Region, Hippocampal

path(MESH:"Alzheimer Disease") positiveCorrelation path(MESH:Depression) View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA3 Region, Hippocampal

path(MESH:"Alzheimer Disease") positiveCorrelation path(MESH:"Cognitive Dysfunction") View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA3 Region, Hippocampal

path(MESH:"Cognitive Dysfunction") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA3 Region, Hippocampal

path(MESH:Apathy) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA3 Region, Hippocampal

path(MESH:Depression) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA3 Region, Hippocampal

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.