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path(MESH:"Neurofibrillary Tangles")

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Entity

Name
Neurofibrillary Tangles
Namespace
MeSH
Namespace Version
20181007
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/01c9daa61012b37dd0a1bc962521ba51a15b38f1/external/mesh-names.belns

Appears in Networks 4

albuquerque2009 v1.0.0

This file encodes the article Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function by Albuquerque et al, 2009

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

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

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

In-Edges 16

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

AD is the most common form of dementia in the elderly population. The histopathology of this disease is well known to have at least four components: 1) loss of cholinergic neurotransmission, 2) deposition of extracellular Abeta peptides into plaques, 3) hyperphosphorylation of the tau protein that leads to excessive formation of neurofibrillar tangles, and 4) increased local inflammation. PubMed:19126755

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a(HBP:"Tau aggregates") increases path(MESH:"Neurofibrillary Tangles") View Subject | View Object

NFTs are formed by accumulation of hyperphosphorylated tau protein[7, 8]. Tau is a microtubule-binding protein whose function is to stabilize microtubules and facilitate fast axonal transport. Once highly phosphorylated, tau dissociates from microtubules and is prone to aggregate, forming paired helical fi laments that aggregate into NFTs PubMed:24590577

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

Recent evidence indicates that cholinergic hypofunction is closely linked to Abeta and tau pathologies[20]. As a major receptor group for ACh, mAChRs have also been implicated in the pathophysiology of AD. PubMed:24590577

Appears in Networks:

path(MESH:"Alzheimer Disease") association path(MESH:"Neurofibrillary Tangles") 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

Appears in Networks:

a(CHEBI:Thrombin) association path(MESH:"Neurofibrillary Tangles") View Subject | View Object

There are also data to suggest that thrombin may act intracellularly to mediate tau pathology. Thrombin is expressed within neurons and astrocytes in both normal and AD brain (38). In AD brain the staining pattern for thrombin and prothrombin was characteristic of the pattern of NFTs, although these structures were not colabeled with antibodies for tau (38). PubMed:24027553

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Annotations
MeSH
Alzheimer Disease
Text Location
Review

a(HBP:"Tau aggregates") increases path(MESH:"Neurofibrillary Tangles") View Subject | View Object

Insoluble, fibrillar intraneuronal accumulations of pathological forms of the tau protein called neurofibrillary tangles (NFTs) are important and defining hallmarks of the Alzheimer disease (AD) brain. Indeed, the progression of AD can be neuropathologically staged based on the location and extent of tau pathology (1). PubMed:24027553

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Text Location
Review

p(HGNC:CAPN2) positiveCorrelation path(MESH:"Neurofibrillary Tangles") View Subject | View Object

The active form of calpain-2 is found in 50–75% of NFTs in tauopathies including AD, but not in protein aggregates found in other diseases (47). This is consistent with another study that found equivalent calpain levels between control and AD cases, but the activity level of the enzyme isolated from AD brain tissue was increased (48). PubMed:24027553

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

p(HGNC:MAPT, frag("1_?")) association path(MESH:"Neurofibrillary Tangles") View Subject | View Object

The predominant post-translational modification of tau in the NFTs is phosphorylation; however numerous modifications have been noted including truncation, acetylation, nitration, and several others (2–4). PubMed:24027553

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Text Location
Review

p(HGNC:MAPT, frag("?_*")) association path(MESH:"Neurofibrillary Tangles") View Subject | View Object

The predominant post-translational modification of tau in the NFTs is phosphorylation; however numerous modifications have been noted including truncation, acetylation, nitration, and several others (2–4). PubMed:24027553

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Annotations
Text Location
Review

p(HGNC:MAPT, pmod(Ac)) association path(MESH:"Neurofibrillary Tangles") View Subject | View Object

The predominant post-translational modification of tau in the NFTs is phosphorylation; however numerous modifications have been noted including truncation, acetylation, nitration, and several others (2–4). PubMed:24027553

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Annotations
Text Location
Review

p(HGNC:MAPT, pmod(HBP:nitration)) association path(MESH:"Neurofibrillary Tangles") View Subject | View Object

The predominant post-translational modification of tau in the NFTs is phosphorylation; however numerous modifications have been noted including truncation, acetylation, nitration, and several others (2–4). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:MAPT, pmod(Ph)) association path(MESH:"Neurofibrillary Tangles") View Subject | View Object

The predominant post-translational modification of tau in the NFTs is phosphorylation; however numerous modifications have been noted including truncation, acetylation, nitration, and several others (2–4). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:MAPT, pmod(Ub)) positiveCorrelation path(MESH:"Neurofibrillary Tangles") View Subject | View Object

However, another study, also using HEK cells and ubiquitin K48 and K63 mutants, demonstrated that in the presence of the E3 ligase CHIP, tau could be ubiquitylated by both K48 and K63 linkages (100). The likelihood that in vivo tau can be ubiquitylated in multiple ways is supported by studies showing tau isolated from NFTs in human brain has several forms of ubiquitin linkages as well as mono-ubiquitylation (101, 102). These data suggest that the physical structure of the ubiquitin chain is unlikely to be a sufficient signal for selectively targeting tau to either the proteasome or autophagy. PubMed:24027553

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Text Location
Review

act(p(HGNCGENEFAMILY:Caspases)) positiveCorrelation path(MESH:"Neurofibrillary Tangles") View Subject | View Object

There was a strong correlation between active caspases and the presence of tangles within viable neurons. In the few cells found that were caspase-positive and tangle-negative, 88% had tangles within 24 h (56). This seems to further support a role for caspase cleavage in the evolution of tau pathology. PubMed:24027553

Appears in Networks:
Annotations
MeSH
Neurons
Text Location
Review

act(p(HGNCGENEFAMILY:Caspases)) association path(MESH:"Neurofibrillary Tangles") 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

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

Insoluble, fibrillar intraneuronal accumulations of pathological forms of the tau protein called neurofibrillary tangles (NFTs) are important and defining hallmarks of the Alzheimer disease (AD) brain. Indeed, the progression of AD can be neuropathologically staged based on the location and extent of tau pathology (1). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

Out-Edges 15

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

AD is the most common form of dementia in the elderly population. The histopathology of this disease is well known to have at least four components: 1) loss of cholinergic neurotransmission, 2) deposition of extracellular Abeta peptides into plaques, 3) hyperphosphorylation of the tau protein that leads to excessive formation of neurofibrillar tangles, and 4) increased local inflammation. PubMed:19126755

Appears in Networks:
Annotations
Text Location
Review

path(MESH:"Neurofibrillary Tangles") biomarkerFor path(MESH:"Alzheimer Disease") View Subject | View Object

The hallmarks of AD pathology are the accumulation of amyloid-beta (Abeta) peptide aggregates (neuritic plaques) and hyperphosphorylated tau protein (neurofibrillary tangles). PubMed:24511233

Appears in Networks:

path(MESH:"Neurofibrillary Tangles") association path(MESH:"Alzheimer Disease") 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

Appears in Networks:

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

Recent evidence indicates that cholinergic hypofunction is closely linked to Abeta and tau pathologies[20]. As a major receptor group for ACh, mAChRs have also been implicated in the pathophysiology of AD. PubMed:24590577

Appears in Networks:

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

Insoluble, fibrillar intraneuronal accumulations of pathological forms of the tau protein called neurofibrillary tangles (NFTs) are important and defining hallmarks of the Alzheimer disease (AD) brain. Indeed, the progression of AD can be neuropathologically staged based on the location and extent of tau pathology (1). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

path(MESH:"Neurofibrillary Tangles") association p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

The predominant post-translational modification of tau in the NFTs is phosphorylation; however numerous modifications have been noted including truncation, acetylation, nitration, and several others (2–4). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

path(MESH:"Neurofibrillary Tangles") association p(HGNC:MAPT, pmod(Ac)) View Subject | View Object

The predominant post-translational modification of tau in the NFTs is phosphorylation; however numerous modifications have been noted including truncation, acetylation, nitration, and several others (2–4). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

path(MESH:"Neurofibrillary Tangles") association p(HGNC:MAPT, pmod(HBP:nitration)) View Subject | View Object

The predominant post-translational modification of tau in the NFTs is phosphorylation; however numerous modifications have been noted including truncation, acetylation, nitration, and several others (2–4). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

path(MESH:"Neurofibrillary Tangles") association p(HGNC:MAPT, frag("1_?")) View Subject | View Object

The predominant post-translational modification of tau in the NFTs is phosphorylation; however numerous modifications have been noted including truncation, acetylation, nitration, and several others (2–4). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

path(MESH:"Neurofibrillary Tangles") association p(HGNC:MAPT, frag("?_*")) View Subject | View Object

The predominant post-translational modification of tau in the NFTs is phosphorylation; however numerous modifications have been noted including truncation, acetylation, nitration, and several others (2–4). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

path(MESH:"Neurofibrillary Tangles") association a(CHEBI:Thrombin) View Subject | View Object

There are also data to suggest that thrombin may act intracellularly to mediate tau pathology. Thrombin is expressed within neurons and astrocytes in both normal and AD brain (38). In AD brain the staining pattern for thrombin and prothrombin was characteristic of the pattern of NFTs, although these structures were not colabeled with antibodies for tau (38). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Alzheimer Disease
Text Location
Review

path(MESH:"Neurofibrillary Tangles") positiveCorrelation p(HGNC:CAPN2) View Subject | View Object

The active form of calpain-2 is found in 50–75% of NFTs in tauopathies including AD, but not in protein aggregates found in other diseases (47). This is consistent with another study that found equivalent calpain levels between control and AD cases, but the activity level of the enzyme isolated from AD brain tissue was increased (48). PubMed:24027553

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

path(MESH:"Neurofibrillary Tangles") positiveCorrelation act(p(HGNCGENEFAMILY:Caspases)) View Subject | View Object

There was a strong correlation between active caspases and the presence of tangles within viable neurons. In the few cells found that were caspase-positive and tangle-negative, 88% had tangles within 24 h (56). This seems to further support a role for caspase cleavage in the evolution of tau pathology. PubMed:24027553

Appears in Networks:
Annotations
MeSH
Neurons
Text Location
Review

path(MESH:"Neurofibrillary Tangles") association act(p(HGNCGENEFAMILY:Caspases)) 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

path(MESH:"Neurofibrillary Tangles") positiveCorrelation p(HGNC:MAPT, pmod(Ub)) View Subject | View Object

However, another study, also using HEK cells and ubiquitin K48 and K63 mutants, demonstrated that in the presence of the E3 ligase CHIP, tau could be ubiquitylated by both K48 and K63 linkages (100). The likelihood that in vivo tau can be ubiquitylated in multiple ways is supported by studies showing tau isolated from NFTs in human brain has several forms of ubiquitin linkages as well as mono-ubiquitylation (101, 102). These data suggest that the physical structure of the ubiquitin chain is unlikely to be a sufficient signal for selectively targeting tau to either the proteasome or autophagy. PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.