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bp(GO:cognition)

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Entity

Name
cognition
Namespace
go
Namespace Version
20180921
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/go-names.belns

Appears in Networks 30

Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease 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

Activation of M1 and M4 muscarinic receptors as potential treatments for Alzheimer's disease and schizophrenia. v1.0.0

This file encodes the article Activation of M1 and M4 muscarinic receptors as potential treatments for Alzheimer’s disease and schizophrenia by Choi et al, 2014

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

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

Nuclear receptors as therapeutic targets for Alzheimer's disease. v1.0.0

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

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

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

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

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

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

Molecular chaperones and regulation of tau quality control: strategies for drug discovery in tauopathies v1.0.0

Tau protein aggregation is associated with cellular senescence in the brain 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

The role of inflammasome in Alzheimer’s disease v1.0.3

Inflammasome Involvement in Alzheimer’s Disease v1.0.0

Amyloid-Binding Alcohol Dehydrogenase (ABAD) Inhibitors for the Treatment of Alzheimer’s Disease v1.0.0

Discriminative Stimulus Properties of S(−)-Nicotine: “A Drug for All Seasons v1.0.0

Protein phosphatase 2A dysfunction in Alzheimer’s disease v1.0.0

Alzheimer’s disease and the autophagic-lysosomal system v1.0.0

The Ubiquitin–Proteasome System and the Autophagic–Lysosomal System in Alzheimer Disease v1.0.0

Tau in physiology and pathology 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

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

mTOR-Related Brain Dysfunctions in Neuropsychiatric Disorders v1.0.0

In-Edges 111

act(a(MESH:"Lymphatic Vessels")) increases bp(GO:cognition) View Subject | View Object

Significant transcriptional alterations were also associated with excitatory synaptic remodelling and plasticity, hippocampal neuronal transmission, learning and memory and ageing-related cognitive decline (Extended Data Fig. 5q, r) PubMed:30046111

Appears in Networks:
Annotations
Confidence
High
MeSH
Meninges

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

The beneficial effect of mVEGF-C treatment in mice from the sham group, which performed significantly better in the NLR (Fig. 2n, o) and MWM (Fig. 2p–r) tests, was abrogated in mice in which the CSF-draining lymphatic vessels had been ligated PubMed:30046111

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Annotations
Confidence
High

p(MGI:Aqp4) increases bp(GO:cognition) View Subject | View Object

Deletion of Aqp4 in transgenic mice with Alzheimer’s disease also resulted in increased amyloid-β plaque burden and exacerbated cognitive impairment PubMed:30046111

Appears in Networks:
Annotations
Confidence
High
MeSH
Alzheimer Disease

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

Agonists of nicotinic ACh receptors can improve, while antagonists for the receptor impair, performance in cognitive tasks PubMed:26813123

Appears in Networks:

path(MESH:"Alzheimer Disease") decreases bp(GO:cognition) View Subject | View Object

AD belongs to a large group of neurodegenerative diseases (NDs) characterized by cognitive impairment and progressive synaptic damage accompanied by neuronal loss. PubMed:29196815

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Annotations
Confidence
High

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

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

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Text Location
Review

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

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

Appears in Networks:
Annotations
MeSH
Hippocampus
Text Location
Review

p(HBP:"alpha-4 beta-2 nAChR") positiveCorrelation bp(GO:cognition) View Subject | View Object

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

Appears in Networks:
Annotations
Text Location
Review

path(MESH:"Alzheimer Disease") negativeCorrelation bp(GO:cognition) View Subject | View Object

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

Appears in Networks:
Annotations
MeSH
Hippocampus
Text Location
Review

a(CHEBI:epibatidine) causesNoChange bp(GO:cognition) View Subject | View Object

The loss of nAChR subunits, as determined by [3H]- epibatidine binding, seems to take place after the transition from mild cognitive impairment (MCI) to AD (Sabbagh et al., 2006), although the loss of epibatidine binding did not correlate with decline in memory, cognitive performance, or with the development of neurofibrillary tangles or plaques (Sabbagh et al., 2001). PubMed:19293145

Appears in Networks:

a(MESH:Synapses) increases bp(GO:cognition) View Subject | View Object

It has long been known that cognitive decline in AD correlates well with synaptic loss (Lue et al., 1999), and it has been shown directly that soluble Abeta inhibits synaptic plasticity (Rowan et al., 2004). PubMed:19293145

Appears in Networks:

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

FYN expression is increased in brains from patients with AD, specifically in a subset of neurons with elevated hyperphosphorylated tau protein (Shirazi and Wood, 1993), but it is not known whether this increase in FYN contributes to hyperphosphorylation of tau or is a protective response to it. In extracts of human brains from patients with AD, soluble FYN increases with cognitive score and synaptophysin levels and inversely with the tangle count, suggestive of a pro-cognitive role for FYN (Ho et al., 2005). PubMed:19293145

Appears in Networks:

path(MESH:"Alzheimer Disease") decreases bp(GO:cognition) View Subject | View Object

Alzheimer’s disease (AD) is the most common form of dementia in elderly persons. It is a neurodegenerative disease marked by decline in memory and cognitive performance, including deterioration of language as well as defects in visual and motor coordination, and eventual death (for review, see Cummings, 2004). PubMed:19293145

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a(CHEBI:"EC 3.1.1.7 (acetylcholinesterase) inhibitor") increases bp(GO:cognition) View Subject | View Object

The current primary treatments for AD symptoms are acetylcholinesterase inhibitors (AChEIs) such as donepezil, tacrine, galantamine, and rivastigmine, which potentiate cholinergic signaling.18,19 These treatments not only provide improvements in cognitive symptoms associated with AD,20,21 but also show efficacy in treating the psychiatric symptoms. PubMed:24511233

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:"antipsychotic agent") causesNoChange bp(GO:cognition) View Subject | View Object

Current treatments include both typical (eg, haloperidol and chlorpromazine) and atypical (eg, risperidone and clozapine) antipsychotics, which act on the dopaminergic system and D2 dopamine receptors in particular. These treatments show partial efficacy in reducing psychotic or positive symptoms;30 however, they demonstrate little to no efficacy in addressing negative symptoms and cognitive impairments, which can prevent patients from participating fully and productively in society PubMed:24511233

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

Of these, the M1/M4 -preferring agonist xanomeline was the only one to progress to a phase III clinical trial, where it was assessed for efficacy in ameliorating cognitive deficits observed in AD patients. While xanomeline showed a trend toward improving cognitive function in these patients, this effect did not reach statistical significance. However, this agonist did produce surprisingly robust and dose-dependent reductions in hallucinations, delusions, vocal outbursts, and other behavioral disturbances in these patients PubMed:24511233

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(MESH:"Cerebral Cortex") association bp(GO:cognition) View Subject | View Object

The popular amyloid cascade hypothesis posits that the gradual build-up of Abeta plaques leads to neuronal inflammation, dysfunction, and, eventually, cell death. The two brain regions most critically affected by this degeneration are the cortex and hippocampus, both of which are involved in cognition, learning, and memory. PubMed:24511233

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(MESH:"Muscarinic Antagonists") decreases bp(GO:cognition) View Subject | View Object

In addition, administration of nonselective muscarinic antagonists can produce or exacerbate cognitive deficits in animals,15 as well as in AD patients and both young and old control subjects,16,17 suggesting that mAChRs can directly modulate cognition. PubMed:24511233

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(MESH:"Prefrontal Cortex") association bp(GO:cognition) View Subject | View Object

In brain slice electrophysiology studies, BQCA enhanced excitatory postsynaptic currents in medial prefrontal cortical neurons,69 an area critical for higher cognitive, learning, and memory functions.70 In pre-clinical animal studies, BQCA reversed scopolamine-impaired contextual fear conditioning and rescued medial prefrontal cortex-dependent discrimination reversal learning deficits in a transgenic mouse model of AD. PubMed:24511233

Appears in Networks:
Annotations
MeSH
Prefrontal Cortex

a(MESH:Hippocampus) association bp(GO:cognition) View Subject | View Object

The popular amyloid cascade hypothesis posits that the gradual build-up of Abeta plaques leads to neuronal inflammation, dysfunction, and, eventually, cell death. The two brain regions most critically affected by this degeneration are the cortex and hippocampus, both of which are involved in cognition, learning, and memory. PubMed:24511233

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Hippocampus

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

1 Several lines of evidence suggest that impaired cholinergic signaling plays a key role in mediating both the cognitive and the behavioral impairments observed in AD patients.12 The basal forebrain cholinergic system is disproportionately affected in AD patients, with a robust loss of cholinergic neurons, including those innervating the hippocampus and cortex. PubMed:24511233

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complex(a(MESH:"GSK 1034702"), p(HGNC:CHRM1)) increases bp(GO:cognition) View Subject | View Object

A recent clinical study utilizing the M1-selective allosteric agonist GSK1034702 demonstrated pro-cognitive efficacy in a nicotine abstinence model of episodic memory impairment in smokers, 67 providing exciting evidence that M1-selective activation can provide pro-cognitive benefits in humans PubMed:24511233

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p(HGNC:CHRM1) association bp(GO:cognition) View Subject | View Object

The M1 mAChR subtype is the most predominantly expressed mAChR subtype in the CNS and is expressed in several brain regions implicated in the regulation of cognitive processes, including the striatum, prefrontal cortex, and hippocampus. PubMed:24511233

Appears in Networks:
Annotations
MeSH
Corpus Striatum
MeSH
Hippocampus
MeSH
Prefrontal Cortex

act(p(HGNC:CHRM1)) increases bp(GO:cognition) View Subject | View Object

Subsequent optimization produced two analogs of AC-42 (AC-260584 and 77-LH-28-1), which maintained M1 selectivity and possessed properties suitable for use in animal models. Both AC-260584 and 77-LH-28-1 displayed antipsychotic and cognition-enhancing efficacy in pre-clinical models PubMed:24511233

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p(HGNCGENEFAMILY:"Cholinergic receptors muscarinic") regulates bp(GO:cognition) View Subject | View Object

In addition, administration of nonselective muscarinic antagonists can produce or exacerbate cognitive deficits in animals,15 as well as in AD patients and both young and old control subjects,16,17 suggesting that mAChRs can directly modulate cognition. PubMed:24511233

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNCGENEFAMILY:"Glutamate ionotropic receptor NMDA type subunits") association bp(GO:cognition) View Subject | View Object

N-methyl-D-aspartate (NMDA) receptors play a critical role in regulating synaptic plasticity, and disrupted NMDA-receptor neurotransmission is thought to underlie the cognitive deficits observed in numerous psychiatric diseases. PubMed:24511233

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path(MESH:"Alzheimer Disease") association bp(GO:cognition) View Subject | View Object

Conversely, the most commonly associated symptoms of AD are cognitive in nature and include deficits in learning and memory. However, 50%–80% of AD patients display psychotic and behavioral disturbances that are correlated with poor social and functional outcomes PubMed:24511233

Appears in Networks:

path(MESH:"Alzheimer Disease") decreases bp(GO:cognition) View Subject | View Object

AD is the most commonly diagnosed form of dementia and currently affects approximately 35 million individuals worldwide.7 AD is a progressive neurodegenerative disease that is characterized by a host of cognitive deficits, including impairments in learning and memory. In addition to the well-documented cognitive impairments, AD patients also display behavioral disturbances, including anxiety, depression, and psychosis PubMed:24511233

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a(CHEBI:"nicotinic acetylcholine receptor agonist") increases bp(GO:cognition) View Subject | View Object

Consistent with these treatments, nicotinic agents improve cognitive deficits of AD patients (20, 158). PubMed:17009926

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

path(MESH:Schizophrenia) association bp(GO:cognition) View Subject | View Object

Psychosis is the hallmark symptom of SZ and manifests as hallucinations, disordered thought/speech, and delusions. While these psychotic symptoms are commonly associated with SZ, it has become well documented that these patients also experience cognitive and behavioral disturbances that are not adequately addressed by currently prescribed typical and atypical psychotics. PubMed:24511233

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

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 PubMed:26813123

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

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 PubMed:26813123

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

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

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 PubMed:26813123

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

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

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 PubMed:26813123

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

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

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 PubMed:26813123

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

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

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 PubMed:26813123

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

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

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 PubMed:26813123

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

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

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 PubMed:26813123

Appears in Networks:

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

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 PubMed:26813123

Appears in Networks:

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

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 PubMed:26813123

Appears in Networks:
Annotations
MeSH
Neocortex
MeSH
Alzheimer Disease

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

Furthermore, cognitive impairment can take place even due to a mild decrease in VAChT protein expression (about 45%) PubMed:26813123

Appears in Networks:

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

One example is xanomeline, an mAChR agonist with selectivity for the M1 and M4 subtypes. Xanomeline improves working memory in rodents and improves cognition and reduces psychotic episodes in AD patients, but it failed during phase-II clinical trial because of serious side-effects, probably due to simultaneous activation of M1 and M4 mAChRs (M4 > M1) PubMed:24590577

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(MESH:"4-(3-(4-butylpiperidin-1-yl)propyl)-7-fluoro-4H-benzo(1,4)oxazin-3-one") increases bp(GO:cognition) View Subject | View Object

The M1 mAChR agonist AC-260584 was recently reported to be orally bioavailable with favorable antipsychotic and cognition-enhancing effects[118, 122]. PubMed:24590577

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a(MESH:"WAY 132983") increases bp(GO:cognition) View Subject | View Object

Similarly, the M1 agonist WAY-132983 at a low dose improves cognitive status in animal models but at a high dose causes side-effects such as salivation and hypothermia[102, 112]. PubMed:24590577

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act(p(HGNC:CHRM1)) increases bp(GO:cognition) View Subject | View Object

Nevertheless, a compound developed later, TBPB, selectively activates M1 mAChR in cell lines and shows no agonist activity in any other mAChR subtype. Interestingly, TBPB also potentiates the NMDA-evoked current in hippocampal pyramidal neurons, which is considered to be important for the effect of M1 mAChR on improving cognition. In addition, TBPB shifts the processing of APP in the non-amyloidogenic direction and thereafter decreases neurotoxic Abeta production vitro[120]. PubMed:24590577

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Pyramidal Cells

p(MGI:Chrm1) increases bp(GO:cognition) View Subject | View Object

Among the mAChR family members, the M1 subtype makes up 50–60% of the total and is predominantly expressed in all major areas of the forebrain, including the hippocampus, cerebral cortex, corpus striatum, and thalamus[36-38]. M1 mAChR-knockout mice show a series of cognitive defi cits and impairments in long-term potentiation, indicating that the M1 subtype is physiologically linked to multiple functions such as synaptic plasticity, neuronal excitability, neuronal differentiation during early development, and learning and memory PubMed:24590577

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path(MESH:"Alzheimer Disease") decreases bp(GO:cognition) View Subject | View Object

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder afflicting millions of people. It is diagnosed by the progressive loss of cognitive function and behavioral defi cits and is characterized by the presence of neurofibrillary tangles (NFTs), senile plaques, cholinergic neuron loss, and neuronal atrophy at autopsy PubMed:24590577

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a(CHEBI:"pregnenolone sulfate") increases bp(GO:cognition) View Subject | View Object

Pregnenolone sulfate (PREGS) is an endogenous steroid known to ameliorate cognitive performance in animals. PREGS is a modulator of synaptic plasticity, acting on the activation of glutamatergic transmission (Smith et al., 2014) PubMed:25514383

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

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

Simvastatin (SV) is a statin commonly used in the clinic to control cholesterol levels and it was shown to improve cognitive function in AD patients (Simons et al., 2002; Sparks et al., 2006) PubMed:25514383

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(HP:"cholinergic neuron") association bp(GO:cognition) View Subject | View Object

Several studies demonstrated the pivotal role of these cholinergic nuclei in cognitive functions PubMed:25514383

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a(HP:"cholinergic neuron") increases bp(GO:cognition) View Subject | View Object

The role of the cholinergic system in cognition and the modification observed in neurodegenerative diseases, and in particular in the case of AD, led to the formulation of the “cholinergic hypothesis” of geriatric disorders (Bartus et al., 1982; Contestabile, 2011), according to which the reduction in cholinergic innervation is responsible for the cognitive decline observed in AD patients PubMed:25514383

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(MESH:"alpha7 Nicotinic Acetylcholine Receptor") increases bp(GO:cognition) View Subject | View Object

It was proposed that the positive action of PREGS is mediated by alpha7 nAChR PubMed:25514383

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(MGI:Chrna7) increases bp(GO:cognition) View Subject | View Object

The authors postulated that the absence of alpha7 could prevent Abeta intracellular accumulation ameliorating the cognitive neuropathology and its phenotypic association (Dziewczapolski et al., 2009) PubMed:25514383

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

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

The neurotransmitter ACh binds to two families of receptors, nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs). Both families of receptors regulate the cognitive processes mentioned above (Ghoneim and Mewaldt, 1977; Petersen, 1977; Sarter and Paolone, 2011), and are both affected in AD PubMed:25514383

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p(FPLX:CHRM) regulates bp(GO:cognition) View Subject | View Object

The neurotransmitter ACh binds to two families of receptors, nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs). Both families of receptors regulate the cognitive processes mentioned above (Ghoneim and Mewaldt, 1977; Petersen, 1977; Sarter and Paolone, 2011), and are both affected in AD PubMed:25514383

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p(MGI:Chrnb2) increases bp(GO:cognition) View Subject | View Object

Null mutant beta2 mice were also tested to determine the role of this subunit in cognition. Guillem et al. (2011) showed that these mice exhibit an attention deficit which was restored by re-expression of this subunit with a lentiviral vector in the PFC PubMed:25514383

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

In this study, pioglitazone treatment was shown to improve memory and cognition in these patients [67,68]. PubMed:21718217

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Annotations
Confidence
High

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

A Phase II clinical trial in which patients were treated with rosiglitazone for 6 months showed improvements in attention and memory retention, but only in patients who did not have an APOE4 allele. PubMed:21718217

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Annotations
Confidence
High

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

As ACh-gated cation channels, these broadly distributed receptors participate in arousal, motivation, and numerous aspects of cognition (Gotti and Clementi, 2004; Hogg et al., 2003; Le Nove` re et al., 2002; Lindstrom, 1997; Picciotto, 2003; Role and Berg, 1996). PubMed:28445721

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

Indeed, presynaptic effects of nAChRs in regulating dopamine release in basal ganglia and prefrontal cortex likely participate in nicotine’s addictive and cognitive effects, respectively (Jasinska et al., 2014) PubMed:28445721

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

Because nAChRs play important roles in cognition (Gotti and Clementi, 2004; Hogg et al., 2003; Le Nove` re et al., 2002; Lindstrom, 1997; Picciotto, 2003; Role and Berg, 1996), we focused attention on this behavi PubMed:28445721

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

However, it is not known whether the nicotine-enhanced cognitive performance exceeds the level that would occur if the person had never begun to smoke, or after remaining abstinent for one year (the usual criterion for successful smoking cessation) (Levin et al., 2006) PubMed:21482353

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a(HBP:"alpha-4 beta-2 nAChR") positiveCorrelation bp(GO:cognition) View Subject | View Object

In rodents and humans, the hippocampus is importantly implicated in cognitive sensitization, and alpha4beta2* nAChRs play key roles (Levin et al., 2006; Davis and Gould, 2009) PubMed:21482353

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

In 2011, we know that cholinergic actions in the brain govern various processes: cognition (attention and executive function) (Couey et al., 2007; Levin and Rezvani, 2007; Heath and Picciotto, 2009; Howe et al., 2010), learning and memory (Gould, 2006; Couey et al., 2007; Levin and Rezvani, 2007), mood (anxiety, depression) (Picciotto et al., 2008), reward (addiction, craving) (Tang and Dani, 2009), and sensory processing (Heath and Picciotto, 2009) PubMed:21482353

Appears in Networks:
Annotations
MeSH
Brain

p(HGNC:CHRNA3, var("?")) positiveCorrelation bp(GO:cognition) View Subject | View Object

Single-nucleotide polymorphisms found in the human alpha5, alpha3, beta4 gene cluster are associated with nicotine dependence and its age-dependent onset; number of cigarettes smoked per day and ‘‘pleasurable buzz’’ elicited by smoking; alcoholism, sensitivity to the depressant effects of alcohol, and age of alcohol initiation; cocaine dependence; opioid dependence; lung cancer; and cognitive flexibility (Erlich et al., 2010; Hansen et al., 2010; Improgo et al., 2010; Saccone et al., 2010; Zhang et al., 2010) PubMed:21482353

Appears in Networks:

p(HGNC:CHRNA5, var("?")) positiveCorrelation bp(GO:cognition) View Subject | View Object

Single-nucleotide polymorphisms found in the human alpha5, alpha3, beta4 gene cluster are associated with nicotine dependence and its age-dependent onset; number of cigarettes smoked per day and ‘‘pleasurable buzz’’ elicited by smoking; alcoholism, sensitivity to the depressant effects of alcohol, and age of alcohol initiation; cocaine dependence; opioid dependence; lung cancer; and cognitive flexibility (Erlich et al., 2010; Hansen et al., 2010; Improgo et al., 2010; Saccone et al., 2010; Zhang et al., 2010) PubMed:21482353

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p(HGNC:CHRNB4, var("?")) positiveCorrelation bp(GO:cognition) View Subject | View Object

Single-nucleotide polymorphisms found in the human alpha5, alpha3, beta4 gene cluster are associated with nicotine dependence and its age-dependent onset; number of cigarettes smoked per day and ‘‘pleasurable buzz’’ elicited by smoking; alcoholism, sensitivity to the depressant effects of alcohol, and age of alcohol initiation; cocaine dependence; opioid dependence; lung cancer; and cognitive flexibility (Erlich et al., 2010; Hansen et al., 2010; Improgo et al., 2010; Saccone et al., 2010; Zhang et al., 2010) PubMed:21482353

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

Interestingly enough, a considerable body of evidence exists to suggest that the nAChRs are involved in cognitive and memory functions (Levin 2000; Newhouse and Kelton 2000; Newhouse et al 1997; Sahakian and Coull 1994) PubMed:11230871

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a(CHEBI:Mecamylamine) decreases bp(GO:cognition) View Subject | View Object

Administration of the nicotinic antagonist mecamylamine to elderly subjects and AD patients has produced cognitive impairment (Newhouse and Kelton 2000) PubMed:11230871

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MeSH
Alzheimer Disease

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

Cholinergic therapy is based on the assumption that low levels of acetylcholine are responsible for the cognitive decline associated with AD PubMed:11230871

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MeSH
Alzheimer Disease

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

Activation of the nAChR modulates the release of several neurotransmitters (Kaiser et al 2000; Wonnacott 1997) that mediate important physiologic mechanisms including cognitive functions PubMed:11230871

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complex(a(CHEBI:nicotine), p(FPLX:CHRN)) association bp(GO:cognition) View Subject | View Object

A significant correlation can be observed between cognitive function and nicotinic receptor binding (k2*) (Figure 3A) PubMed:11230871

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path(MESH:"Alzheimer Disease") negativeCorrelation bp(GO:cognition) 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

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MeSH
Cerebral Cortex

a(CHEBI:Mecamylamine) decreases bp(GO:cognition) View Subject | View Object

early studies indicated that acute nicotine administration improved performance of patients with Alzheimer’s disease in cognitive tasks, whereas acute administration of the non-competitive (channel blocker) antagonist mecamylamine resulted in dose-dependent impairment of performance in a battery of cognitive tasks137–141 PubMed:19721446

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MeSH
Alzheimer Disease
Text Location
Review

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

early studies indicated that acute nicotine administration improved performance of patients with Alzheimer’s disease in cognitive tasks, whereas acute administration of the non-competitive (channel blocker) antagonist mecamylamine resulted in dose-dependent impairment of performance in a battery of cognitive tasks137–141 PubMed:19721446

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Alzheimer Disease
Text Location
Review

a(DRUGBANK:Facinicline) increases bp(GO:cognition) View Subject | View Object

Two partial agonists of alpha7 nAChRs, GTS-21 (also a strong alpha4beta2 antagonist) and MeM-3454 (also a strong 5-hydroxytryptamine type 3 receptor (5HT3) antagonist)149 (TABLe 1), further showed a procognitive action and, in preclinical studies, MeM-3454 enhanced episodic, spatial and working memory. PubMed:19721446

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Review

a(MESH:"3-(2,4-dimethoxybenzylidene)anabaseine") increases bp(GO:cognition) View Subject | View Object

Two partial agonists of alpha7 nAChRs, GTS-21 (also a strong alpha4beta2 antagonist) and MeM-3454 (also a strong 5-hydroxytryptamine type 3 receptor (5HT3) antagonist)149 (TABLe 1), further showed a procognitive action and, in preclinical studies, MeM-3454 enhanced episodic, spatial and working memory. PubMed:19721446

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Text Location
Review

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

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

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MeSH
Hippocampus
MeSH
Alzheimer Disease
Text Location
Review

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

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

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MeSH
Alzheimer Disease
Text Location
Review

path(MESH:"Alzheimer Disease") decreases bp(GO:cognition) View Subject | View Object

Alzheimer’s disease is characterized by progressive cognitive decline, accompanied by a loss of neurons and synapses — especially cholinergic synapses — in the basal forebrain, cerebral cortex and hippocampus126 and by a substantial reduction in both muscarinic and nicotinic AChR expression127. PubMed:19721446

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MeSH
Basal Forebrain
MeSH
Cerebral Cortex
MeSH
Hippocampus
Text Location
Review

path(MESH:Schizophrenia) association bp(GO:cognition) View Subject | View Object

in addition to the obvious symptoms of hallucinations and delusions, patients with schizophrenia frequently suffer from cognitive symptoms, such as the inability to focus attention173. PubMed:19721446

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Review

a(CHEBI:"alpha,alpha-trehalose") increases bp(GO:cognition) View Subject | View Object

It also proved effective in cellu- lar models of PD, HD and AD 121,122 , as well as in mouse models of HD, AD and tauopathies, where it cleared aggregates, reduced neurodegeneration and ameliorated motor and cognitive performance 123–125 . PubMed:30116051

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MeSH
Dopaminergic Neurons

a(CHEBI:"epothilone D") increases bp(GO:cognition) View Subject | View Object

Furthermore, epothilone D countered microtubule disruption and cognitive deficits in aged P301S/P19 AD mice 183 . PubMed:30116051

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MeSH
Machado-Joseph Disease

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

Cilostazol improved cognition and reduced levels of Aβ42 and hyperphosphorylated tau following intra- cerebroventricular injection of Aβ25–35 into mice 162,163 . PubMed:30116051

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MeSH
Machado-Joseph Disease

p(HBP:"Tau C3") negativeCorrelation bp(GO:cognition) View Subject | View Object

Furthermore, active caspase co-localizes to NFTs (58), and caspase-cleaved tau is found in AD-affected brain regions, particularly in neurons displaying tangle pathology (59, 60). This includes tau cleaved by caspase-6 in the C-terminus (58–60) as well as in the N-terminus (24). TauC3 is present in AD brain – in neurons and co-localized with NFTs – and inversely correlates with cognitive function (55, 60, 61). PubMed:24027553

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MeSH
Alzheimer Disease
Text Location
Review

a(CHEBI:"NMDA receptor antagonist") positiveCorrelation bp(GO:cognition) View Subject | View Object

There are no cures for any tauopathy. Neuroprotective agents, such as acetylcholinesterase inhibitors and NMDA antagonists, have been approved for use in the clinic, based on their ability to slow the rate of cognitive decline in patients with moderate to severe AD (reviewed in [36]) PubMed:21882945

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MeSH
Alzheimer Disease

a(PUBCHEM:134222899) positiveCorrelation bp(GO:cognition) View Subject | View Object

There are no cures for any tauopathy. Neuroprotective agents, such as acetylcholinesterase inhibitors and NMDA antagonists, have been approved for use in the clinic, based on their ability to slow the rate of cognitive decline in patients with moderate to severe AD (reviewed in [36]) PubMed:21882945

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MeSH
Alzheimer Disease

path(MESH:Tauopathies) negativeCorrelation bp(GO:cognition) View Subject | View Object

For example, tau pathology closely correlates to neuron loss and cognitive deficits PubMed:21882945

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a(GO:"neurofibrillary tangle") decreases bp(GO:cognition) View Subject | View Object

Tau-containing neurofibrillary tangle (NFT) accumulation is the closest correlate with cognitive decline and cell loss (Arriagada et al., 1992), yet mechanisms mediating tau toxicity are poorly understood PubMed:30126037

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Confidence
High

a(HBP:"Tau oligomers") decreases bp(GO:cognition) View Subject | View Object

When tau oligomers, rather than tau monomers or fibrils, are injected into the brain of wild-type mice, cognitive, synaptic, and mitochondrial abnormalities follow (Lasagna- Reeves et al., 2011; Castillo-Carranza et al., 2014b) PubMed:28420982

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Confidence
High
MeSH
Cerebral Cortex

p(MGI:Casp1) decreases bp(GO:cognition) View Subject | View Object

In support, knockout of NLRP3 and caspase-1 have been shown to suppress amyloidogenesis and neuropathology, and improve cognition in AD transgenic mice (Heneka et al., 2013) PubMed:24561250

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Confidence
High
MeSH
Alzheimer Disease
NeuroMMSigDB
Caspase subgraph

p(MGI:Nlrp3) decreases bp(GO:cognition) View Subject | View Object

In support, knockout of NLRP3 and caspase-1 have been shown to suppress amyloidogenesis and neuropathology, and improve cognition in AD transgenic mice (Heneka et al., 2013) PubMed:24561250

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Confidence
High
MeSH
Alzheimer Disease
NeuroMMSigDB
Caspase subgraph

path(MESH:Periodontitis) decreases bp(GO:cognition) View Subject | View Object

Longitudinal studies including that by Ide et al. [8] all agree that in AD, the presence of periodonti- tis appears to be associated with a marked increase in cognitive decline. PubMed:27314526

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Confidence
High
MeSH
Brain
MeSH
Alzheimer Disease

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

Only five drugs (Figure 1) have been approved by the U. S. Food and Drug Administration (FDA), four of which are cholinesterase inhibitors (tacrine, 15 donepezil, 16 rivastigmine 17 and galantamine 18 ) and one of which is a N-methyl-D-aspartate (NMDA) receptor antagonist (memantine 19 ). a N-methyl-D-aspartate (NMDA) receptor antagonist (memantine 19 ). These pharmacological agents have had limited effect in improving the cognitive function of AD patients and do not slow the progression of the disease. Clinical studies have shown that these agents temporarily stabilize cognitive impairment and help to maintain global function, delaying the need for patient palliative care by only a few month PubMed:30444369

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MeSH
Alzheimer Disease

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

Only five drugs (Figure 1) have been approved by the U. S. Food and Drug Administration (FDA), four of which are cholinesterase inhibitors (tacrine, 15 donepezil, 16 rivastigmine 17 and galantamine 18 ) and one of which is a N-methyl-D-aspartate (NMDA) receptor antagonist (memantine 19 ). a N-methyl-D-aspartate (NMDA) receptor antagonist (memantine 19 ). These pharmacological agents have had limited effect in improving the cognitive function of AD patients and do not slow the progression of the disease. Clinical studies have shown that these agents temporarily stabilize cognitive impairment and help to maintain global function, delaying the need for patient palliative care by only a few month PubMed:30444369

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MeSH
Alzheimer Disease

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

Only five drugs (Figure 1) have been approved by the U. S. Food and Drug Administration (FDA), four of which are cholinesterase inhibitors (tacrine, 15 donepezil, 16 rivastigmine 17 and galantamine 18 ) and one of which is a N-methyl-D-aspartate (NMDA) receptor antagonist (memantine 19 ). a N-methyl-D-aspartate (NMDA) receptor antagonist (memantine 19 ). These pharmacological agents have had limited effect in improving the cognitive function of AD patients and do not slow the progression of the disease. Clinical studies have shown that these agents temporarily stabilize cognitive impairment and help to maintain global function, delaying the need for patient palliative care by only a few month PubMed:30444369

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MeSH
Alzheimer Disease

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

Only five drugs (Figure 1) have been approved by the U. S. Food and Drug Administration (FDA), four of which are cholinesterase inhibitors (tacrine, 15 donepezil, 16 rivastigmine 17 and galantamine 18 ) and one of which is a N-methyl-D-aspartate (NMDA) receptor antagonist (memantine 19 ). a N-methyl-D-aspartate (NMDA) receptor antagonist (memantine 19 ). These pharmacological agents have had limited effect in improving the cognitive function of AD patients and do not slow the progression of the disease. Clinical studies have shown that these agents temporarily stabilize cognitive impairment and help to maintain global function, delaying the need for patient palliative care by only a few month PubMed:30444369

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MeSH
Alzheimer Disease

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

Only five drugs (Figure 1) have been approved by the U. S. Food and Drug Administration (FDA), four of which are cholinesterase inhibitors (tacrine, 15 donepezil, 16 rivastigmine 17 and galantamine 18 ) and one of which is a N-methyl-D-aspartate (NMDA) receptor antagonist (memantine 19 ). a N-methyl-D-aspartate (NMDA) receptor antagonist (memantine 19 ). These pharmacological agents have had limited effect in improving the cognitive function of AD patients and do not slow the progression of the disease. Clinical studies have shown that these agents temporarily stabilize cognitive impairment and help to maintain global function, delaying the need for patient palliative care by only a few month PubMed:30444369

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MeSH
Alzheimer Disease

path(MESH:"Smoking Cessation") decreases bp(GO:cognition) View Subject | View Object

(-)-Nicotine withdrawal symptoms might begin within a few hours after the last nicotine product, and include irritability/anger/stress/anxiety, sleep disturbances, depressed mood, craving, cognitive and attention deficits, and increased appetite. PubMed:28391535

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a(CHEBI:"okadaic acid") decreases bp(GO:cognition) View Subject | View Object

In vivo use of phosphatase inhibitors such as okadaic acid has been shown in many studies to induce cognitive impairment and widespread neurotoxic effects that are reminiscent of the hallmark pathological processes occurring in AD pathology, i.e., the accumulation of P-tau, amyloidogenesis, synapse loss and neurodegeneration (Malchiodi-Albedi et al., 1997; Arendt et al., 1998; Sun et al.,2003; Kamat et al.,2013) PubMed:24653673

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bp(GO:"one-carbon metabolic process") decreases bp(GO:cognition) View Subject | View Object

Remarkably, impairment of one-carbon metabolism in animal models can reproduce AD-like pathological features: accumulation of P-tau (Sontag et al.,2007; Zhang et al.,2008; Wei et al.,2011); enhanced amyloidogenesis (Pacheco-Quinto et al.,2006; Zhang et al.,2009; Zhuo et al.,2010; Zhuo and Pratico,2010); increased phosphorylation of APP at the regulatory Thr-668 site (Sontag et al.,2007; Zhang et al.,2009); increased sensitivity to amyloid toxicity (Kruman et al.,2002); and cognitive impairment (Bernardo et al.,2007; Wei et al.,2011; Rhodehouse et al., 2013). PubMed:24653673

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

Paclitaxel reversed Aβ-induced microtubule disruption and restored autophagosomal transport in neurons [161], while a similar compound, epothilone D/BMS-241027, reduced tauopathy and improved cognition in P301S transgenic mice [162] although the compound did not progress beyond Phase I clinical testing PubMed:29758300

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

For instance, rapamycin, an inhibitor of the Ser/Thr protein kinase mammalian target of rapamycin (mTOR), improves cognitive function and reduces Aβ in AD mouse model by enhancing autophagic flux [23]. PubMed:29758300

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deg(p(HGNC:MAPT, pmod(Ph))) increases bp(GO:cognition) View Subject | View Object

TFEB has been shown to effectively clear phosphorylated tau proteins through A-LS, resulting in ameliorated neuronal loss and neuroinflammation, as well as improved cognitive performance [89]. PubMed:29758300

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act(a(GO:synapse)) positiveCorrelation bp(GO:cognition) View Subject | View Object

Synaptic loss has long been documented in AD brain (Gonatas et al. 1967) and, as expected, is strongly correlated with the degree of cognitive impairment (Terry et al. 1991). PubMed:22908190

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MeSH
Brain

p(HGNC:MAPT, var("p.Lys280del")) decreases bp(GO:cognition) View Subject | View Object

The pro-aggregant mouse lines developed AD‑like features (including missorting of tau into the somatodendritic compartment, tau conformational changes, tau hyperphosphorylation, NFTs and cognitive deficits), whereas the anti-aggregant lines show almost no pathology PubMed:26631930

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complex(GO:"NF-kappaB complex") regulates bp(GO:cognition) View Subject | View Object

Given the indispensable role of NF-κB proteins in synaptic transmission and synaptic plasticity, it is not surprising that NF-κB is plays an indispensable role in cognition and behavior as well PubMed:28745240

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MeSH
Alzheimer Disease

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

Salidroside ameliorated cognitive injury in an AD rat model by regulating the expressions of thioredoxin, thioredoxin interacting protein and NF-B pathway proteins such as NF-B p65, IB, IKK and IKK[137]. PubMed:29179999

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MeSH
Alzheimer Disease

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

Besides, it attenuated cognitive disorders nd inflam-matory reactions in A 1-42-activated AD mice[194]. PubMed:29179999

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MeSH
Alzheimer Disease

a(PUBCHEM:9832404) increases bp(GO:cognition) View Subject | View Object

On the other hand, chronic treatment with an eight-amino-acid peptide snippet from ADNP (NAP), also known as davunetide, restored both Beclin1 and ADNP mRNA levels along with ADNP-LC3 interaction, thus providing neuroprotection while ameliorating schizophrenic-like behavioral and cognitive deficits in Map6+/- mice PubMed:30061532

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MeSH
Schizophrenia

act(p(HGNC:MTOR)) decreases bp(GO:cognition) View Subject | View Object

On the other hand, some evidence indicates that suppressing mTOR activity ameliorates AD cognitive defects by decreasing Abeta and tau pathology PubMed:30061532

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MeSH
Alzheimer Disease

Out-Edges 35

bp(GO:cognition) positiveCorrelation p(HBP:"alpha-4 beta-2 nAChR") View Subject | View Object

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

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Review

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

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

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Review

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

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

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MeSH
Hippocampus
Text Location
Review

bp(GO:cognition) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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

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MeSH
Hippocampus
Text Location
Review

bp(GO:cognition) association p(HGNCGENEFAMILY:"Glutamate ionotropic receptor NMDA type subunits") View Subject | View Object

N-methyl-D-aspartate (NMDA) receptors play a critical role in regulating synaptic plasticity, and disrupted NMDA-receptor neurotransmission is thought to underlie the cognitive deficits observed in numerous psychiatric diseases. PubMed:24511233

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bp(GO:cognition) association path(MESH:Schizophrenia) View Subject | View Object

Psychosis is the hallmark symptom of SZ and manifests as hallucinations, disordered thought/speech, and delusions. While these psychotic symptoms are commonly associated with SZ, it has become well documented that these patients also experience cognitive and behavioral disturbances that are not adequately addressed by currently prescribed typical and atypical psychotics. PubMed:24511233

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bp(GO:cognition) association path(MESH:"Alzheimer Disease") View Subject | View Object

Conversely, the most commonly associated symptoms of AD are cognitive in nature and include deficits in learning and memory. However, 50%–80% of AD patients display psychotic and behavioral disturbances that are correlated with poor social and functional outcomes PubMed:24511233

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bp(GO:cognition) association a(MESH:Hippocampus) View Subject | View Object

The popular amyloid cascade hypothesis posits that the gradual build-up of Abeta plaques leads to neuronal inflammation, dysfunction, and, eventually, cell death. The two brain regions most critically affected by this degeneration are the cortex and hippocampus, both of which are involved in cognition, learning, and memory. PubMed:24511233

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MeSH
Cerebral Cortex
MeSH
Hippocampus

bp(GO:cognition) association a(MESH:"Cerebral Cortex") View Subject | View Object

The popular amyloid cascade hypothesis posits that the gradual build-up of Abeta plaques leads to neuronal inflammation, dysfunction, and, eventually, cell death. The two brain regions most critically affected by this degeneration are the cortex and hippocampus, both of which are involved in cognition, learning, and memory. PubMed:24511233

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MeSH
Cerebral Cortex
MeSH
Hippocampus

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

1 Several lines of evidence suggest that impaired cholinergic signaling plays a key role in mediating both the cognitive and the behavioral impairments observed in AD patients.12 The basal forebrain cholinergic system is disproportionately affected in AD patients, with a robust loss of cholinergic neurons, including those innervating the hippocampus and cortex. PubMed:24511233

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bp(GO:cognition) association p(HGNC:CHRM1) View Subject | View Object

The M1 mAChR subtype is the most predominantly expressed mAChR subtype in the CNS and is expressed in several brain regions implicated in the regulation of cognitive processes, including the striatum, prefrontal cortex, and hippocampus. PubMed:24511233

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MeSH
Corpus Striatum
MeSH
Hippocampus
MeSH
Prefrontal Cortex

bp(GO:cognition) association a(MESH:"Prefrontal Cortex") View Subject | View Object

In brain slice electrophysiology studies, BQCA enhanced excitatory postsynaptic currents in medial prefrontal cortical neurons,69 an area critical for higher cognitive, learning, and memory functions.70 In pre-clinical animal studies, BQCA reversed scopolamine-impaired contextual fear conditioning and rescued medial prefrontal cortex-dependent discrimination reversal learning deficits in a transgenic mouse model of AD. PubMed:24511233

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MeSH
Prefrontal Cortex

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

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 PubMed:26813123

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

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 PubMed:26813123

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

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 PubMed:26813123

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bp(GO:cognition) association a(HP:"cholinergic neuron") View Subject | View Object

Several studies demonstrated the pivotal role of these cholinergic nuclei in cognitive functions PubMed:25514383

Appears in Networks:

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

As ACh-gated cation channels, these broadly distributed receptors participate in arousal, motivation, and numerous aspects of cognition (Gotti and Clementi, 2004; Hogg et al., 2003; Le Nove` re et al., 2002; Lindstrom, 1997; Picciotto, 2003; Role and Berg, 1996). PubMed:28445721

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

Because nAChRs play important roles in cognition (Gotti and Clementi, 2004; Hogg et al., 2003; Le Nove` re et al., 2002; Lindstrom, 1997; Picciotto, 2003; Role and Berg, 1996), we focused attention on this behavi PubMed:28445721

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

In 2011, we know that cholinergic actions in the brain govern various processes: cognition (attention and executive function) (Couey et al., 2007; Levin and Rezvani, 2007; Heath and Picciotto, 2009; Howe et al., 2010), learning and memory (Gould, 2006; Couey et al., 2007; Levin and Rezvani, 2007), mood (anxiety, depression) (Picciotto et al., 2008), reward (addiction, craving) (Tang and Dani, 2009), and sensory processing (Heath and Picciotto, 2009) PubMed:21482353

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MeSH
Brain

bp(GO:cognition) positiveCorrelation a(HBP:"alpha-4 beta-2 nAChR") View Subject | View Object

In rodents and humans, the hippocampus is importantly implicated in cognitive sensitization, and alpha4beta2* nAChRs play key roles (Levin et al., 2006; Davis and Gould, 2009) PubMed:21482353

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bp(GO:cognition) positiveCorrelation p(HGNC:CHRNA5, var("?")) View Subject | View Object

Single-nucleotide polymorphisms found in the human alpha5, alpha3, beta4 gene cluster are associated with nicotine dependence and its age-dependent onset; number of cigarettes smoked per day and ‘‘pleasurable buzz’’ elicited by smoking; alcoholism, sensitivity to the depressant effects of alcohol, and age of alcohol initiation; cocaine dependence; opioid dependence; lung cancer; and cognitive flexibility (Erlich et al., 2010; Hansen et al., 2010; Improgo et al., 2010; Saccone et al., 2010; Zhang et al., 2010) PubMed:21482353

Appears in Networks:

bp(GO:cognition) positiveCorrelation p(HGNC:CHRNA3, var("?")) View Subject | View Object

Single-nucleotide polymorphisms found in the human alpha5, alpha3, beta4 gene cluster are associated with nicotine dependence and its age-dependent onset; number of cigarettes smoked per day and ‘‘pleasurable buzz’’ elicited by smoking; alcoholism, sensitivity to the depressant effects of alcohol, and age of alcohol initiation; cocaine dependence; opioid dependence; lung cancer; and cognitive flexibility (Erlich et al., 2010; Hansen et al., 2010; Improgo et al., 2010; Saccone et al., 2010; Zhang et al., 2010) PubMed:21482353

Appears in Networks:

bp(GO:cognition) positiveCorrelation p(HGNC:CHRNB4, var("?")) View Subject | View Object

Single-nucleotide polymorphisms found in the human alpha5, alpha3, beta4 gene cluster are associated with nicotine dependence and its age-dependent onset; number of cigarettes smoked per day and ‘‘pleasurable buzz’’ elicited by smoking; alcoholism, sensitivity to the depressant effects of alcohol, and age of alcohol initiation; cocaine dependence; opioid dependence; lung cancer; and cognitive flexibility (Erlich et al., 2010; Hansen et al., 2010; Improgo et al., 2010; Saccone et al., 2010; Zhang et al., 2010) PubMed:21482353

Appears in Networks:

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

Interestingly enough, a considerable body of evidence exists to suggest that the nAChRs are involved in cognitive and memory functions (Levin 2000; Newhouse and Kelton 2000; Newhouse et al 1997; Sahakian and Coull 1994) PubMed:11230871

Appears in Networks:

bp(GO:cognition) 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

bp(GO:cognition) association complex(a(CHEBI:nicotine), p(FPLX:CHRN)) View Subject | View Object

A significant correlation can be observed between cognitive function and nicotinic receptor binding (k2*) (Figure 3A) PubMed:11230871

Appears in Networks:

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

Cholinergic therapy is based on the assumption that low levels of acetylcholine are responsible for the cognitive decline associated with AD PubMed:11230871

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

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

Activation of the nAChR modulates the release of several neurotransmitters (Kaiser et al 2000; Wonnacott 1997) that mediate important physiologic mechanisms including cognitive functions PubMed:11230871

Appears in Networks:

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

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

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

bp(GO:cognition) association path(MESH:Schizophrenia) View Subject | View Object

in addition to the obvious symptoms of hallucinations and delusions, patients with schizophrenia frequently suffer from cognitive symptoms, such as the inability to focus attention173. PubMed:19721446

Appears in Networks:
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Text Location
Review

bp(GO:cognition) negativeCorrelation path(MESH:Tauopathies) View Subject | View Object

For example, tau pathology closely correlates to neuron loss and cognitive deficits PubMed:21882945

Appears in Networks:

bp(GO:cognition) negativeCorrelation p(HBP:"Tau C3") View Subject | View Object

Furthermore, active caspase co-localizes to NFTs (58), and caspase-cleaved tau is found in AD-affected brain regions, particularly in neurons displaying tangle pathology (59, 60). This includes tau cleaved by caspase-6 in the C-terminus (58–60) as well as in the N-terminus (24). TauC3 is present in AD brain – in neurons and co-localized with NFTs – and inversely correlates with cognitive function (55, 60, 61). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Alzheimer Disease
Text Location
Review

bp(GO:cognition) positiveCorrelation a(PUBCHEM:134222899) View Subject | View Object

There are no cures for any tauopathy. Neuroprotective agents, such as acetylcholinesterase inhibitors and NMDA antagonists, have been approved for use in the clinic, based on their ability to slow the rate of cognitive decline in patients with moderate to severe AD (reviewed in [36]) PubMed:21882945

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

bp(GO:cognition) positiveCorrelation a(CHEBI:"NMDA receptor antagonist") View Subject | View Object

There are no cures for any tauopathy. Neuroprotective agents, such as acetylcholinesterase inhibitors and NMDA antagonists, have been approved for use in the clinic, based on their ability to slow the rate of cognitive decline in patients with moderate to severe AD (reviewed in [36]) PubMed:21882945

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

bp(GO:cognition) positiveCorrelation act(a(GO:synapse)) View Subject | View Object

Synaptic loss has long been documented in AD brain (Gonatas et al. 1967) and, as expected, is strongly correlated with the degree of cognitive impairment (Terry et al. 1991). PubMed:22908190

Appears in Networks:
Annotations
MeSH
Brain

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.