1. Catalog
  2. Nodes
  3. a(GO:"neurofibrillary tangle")

a(GO:"neurofibrillary tangle")

Equivalencies: 0 | Classes: 0 | Children: 1 | Explore

Entity

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

Appears in Networks 18

Amyloid β oligomers (AβOs) in Alzheimer’s disease v1.0.0

APP processing in Alzheimer's disease v1.0.1

APP processing in Alzheimer's disease

Adenosine A1 receptor antagonist 64627 alleviates axonopathy caused by human Tau ΔK280 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

Tau Protein Hyperphosphorylation and Aggregation in Alzheimer’s Disease and Other Tauopathies, and Possible Neuroprotective Strategies v1.0.0

Tau oligomers and tau toxicity in neurodegenerative disease v1.0.0

Tau oligomers and tau toxicity in neurodegenerative disease by Ward et al., 2012

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

Anatabine Attenuates Tau Phosphorylation and Oligomerization in P301S Tau Transgenic Mice v1.0.0

Assembly and structure of protein phosphatase 2A 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

Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection v1.0.0

Carboxy terminus heat shock protein 70 interacting protein reduces tau-associated degenerative changes v1.0.0

Tau in physiology and pathology v1.0.0

New insights into the role of microRNAs and long noncoding RNAs in most common neurodegenerative diseases v1.0.0

Significance of NF-κB as a pivotal therapeutic target in the neurodegenerative pathologies of Alzheimer's disease and multiple sclerosis v1.0.0

In-Edges 74

path(MESH:"Alzheimer Disease") positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

The histopathological changes in the brain include the presence of extracellular amyloid plaques consisted of various peptide variants of amyloid β (Aβ) and accumulation of intracellular neurofibrillary tangles (NFTs) composed mainly of phosphorylated Tau proteins (pTau), localized predominantly in neurons (reviewed by Serrano-Pozo et al. 2011). PubMed:29196815

Appears in Networks:
Annotations
Confidence
Medium

p(HGNC:MAPT, pmod(Ph)) increases a(GO:"neurofibrillary tangle") View Subject | View Object

The neurofibrillary tangles (NFTs) consist largely of hyperphosphorylated twisted filaments of the microtubule-associated protein tau [4,5] PubMed:21214928

Appears in Networks:
Annotations
Confidence
High

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) causesNoChange a(GO:"neurofibrillary tangle") View Subject | View Object

MC-1–positive Tau accumulates in the axonal grains of proaggregant Tau as described above (arrowheads), whereas antiaggregant slices remain unstained PubMed:27671637

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

MC-1–positive Tau accumulates in the axonal grains of proaggregant Tau as described above (arrowheads), whereas antiaggregant slices remain unstained PubMed:27671637

Appears in Networks:

a(CHEBI:Anatabine) decreases a(GO:"neurofibrillary tangle") View Subject | View Object

Moreover, a significant reduction in MC1-immunoreactivity (P<0.05) was observed in the detergent soluble and insoluble fractions of brain and spinal cord homogenates from Tg Tau P301S mice treated with anatabine showing that anatabine prevents the formation of pathological tau conformers (Figure 7). DOI:10.4172/2168-975X.1000126

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Spinal Cord

bp(GO:"cellular senescence") increases a(GO:"neurofibrillary tangle") View Subject | View Object

Tau transgenic mice with late stage pathology were treated with senolytics to remove senescent cells. Despite the advanced age and disease progression, MRI brain imaging and histopathological analyses indicated a reduction in total NFT density, neuron loss and ventricular enlargement PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Alzheimer Disease

bp(GO:"cellular senescence") association a(GO:"neurofibrillary tangle") View Subject | View Object

Collectively, these findings indicate a strong association between the presence of NFTs and cellular senescence in the brain, which contributes to neurodegeneration PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Brain
MeSH
Alzheimer Disease

composite(a(CHEBI:"dasatinib (anhydrous)"), a(CHEBI:quercetin)) decreases a(GO:"neurofibrillary tangle") View Subject | View Object

Consistent with senescent cell removal, intermittent DQ treatment significantly reduced the number of NFT-containing cortical neurons (P < 0.0001, 5% reduction; Figure 5a,b) PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

composite(a(CHEBI:"dasatinib (anhydrous)"), a(CHEBI:quercetin)) decreases a(GO:"neurofibrillary tangle") View Subject | View Object

The DQ-dependent reduction in cortical NFTs corresponded with decreased ventricular volume pathology (28% decrease, P = 0.05, Figure 5d, f) and a reduction in cortical brain atrophy (compared to controls: P = 0.0092 and P = 0.0274, vehicle and DQ, respectively; Figure S5a) PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

composite(a(CHEBI:"dasatinib (anhydrous)"), a(CHEBI:quercetin)) decreases a(GO:"neurofibrillary tangle") View Subject | View Object

The astrocyte protein GFAP was unchanged, while microglia Iba1 expression was elevated (Iba1: 40%, P = 0.0013; Figure S6b-d) suggesting that DQ-mediated neuroprotection and decreased SASP was not derived from a reduction in pro-inflammatory glia (astrocytes or microglia) but instead associated with fewer NFT-containing neurons PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:CDKN2A) association a(GO:"neurofibrillary tangle") View Subject | View Object

Similarly, elevated expression of the cyclin dependent kinase inhibitor 2a, Cdkn2a, is one of the most robust markers of cellular senescence, and its protein product, p16INK4A, co-localizes with NFTs in human AD (Arendt et al., 1996) PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

p(HGNC:CDKN2A) positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

Consistent with the results from transgenic mice, CDKN2A was upregulated in PSP brains (P = 0.0415, Figure 4g) and expression correlated with NFT deposition, specifically in the parietal lobe (ANOVA, P = 0.0008; Kendall’s Tau rank correlation P = 0.059, Figure 4h) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Parietal Lobe
MeSH
Supranuclear Palsy, Progressive

p(MGI:Cdkn2a) positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

Cdkn2a transcript level, a hallmark measure of senescence, directly correlated with brain atrophy and NFT burden in mice PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Alzheimer Disease

p(MGI:Mapt) increases a(GO:"neurofibrillary tangle") View Subject | View Object

However, genetically ablating endogenous mouse tau (microtubule associated protein tau, Mapt) reduces NFT pathology and neurodegeneration in tauNFT mice (tauNFT-Mapt0/0) (Wegmann et al., 2015) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

p(MGI:Mapt, var("p.Pro301Leu")) increases a(GO:"neurofibrillary tangle") View Subject | View Object

TauNFT mice develop aggressive tauopathy with NFT formation in early life, and show a senescence-associated transcriptomic profile with NFT onset (Figure 1c) PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

path(HP:"Brain atrophy") association a(GO:"neurofibrillary tangle") View Subject | View Object

NFTs are highly correlated with the rate of ventricular enlargement, an indicator of brain atrophy and hallmark of AD pathology (Silbert et al., 2003) PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

path(MESH:"Hypertrophy, Left Ventricular") association a(GO:"neurofibrillary tangle") View Subject | View Object

NFTs are highly correlated with the rate of ventricular enlargement, an indicator of brain atrophy and hallmark of AD pathology (Silbert et al., 2003) PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

path(MESH:"Hypertrophy, Right Ventricular") association a(GO:"neurofibrillary tangle") View Subject | View Object

NFTs are highly correlated with the rate of ventricular enlargement, an indicator of brain atrophy and hallmark of AD pathology (Silbert et al., 2003) PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

path(MESH:"Supranuclear Palsy, Progressive") increases a(GO:"neurofibrillary tangle") View Subject | View Object

PSP is an age-associated tauopathy that clinically manifests as parkinsonism with additional motor abnormalities and cognitive dysfunction (Orr et al., 2017), and is neuropathologically defined by accumulation of four-repeat (4R) tau, NFTs, gliosis and neurodegeneration (Flament et al., 1991) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Supranuclear Palsy, Progressive

a(HBP:"Tau fibrils") increases a(GO:"neurofibrillary tangle") View Subject | View Object

As these granular tau oligomers fuse together, they form tau fibrils, which ultimately form NFTs (Takashima, 2013) PubMed:28420982

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

a(HBP:"Tau aggregates") increases a(GO:"neurofibrillary tangle") View Subject | View Object

These share a common histopathological hallmark known as neurofibrillary tangles (NFTs) that consist of an accumulation of fibrillar tau deposits initially produced from tau protein aggregation (Ballatore et al., 2007) PubMed:28420982

Appears in Networks:
Annotations
Confidence
High

p(HGNC:MAPT, pmod(Ph)) increases a(GO:"neurofibrillary tangle") View Subject | View Object

Hyper-phosphorylated tau assembles into small aggregates known as tau oligomers in route of NFT formation PubMed:28420982

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex

path(MESH:"Alzheimer Disease") positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

Compared to non-demented controls, AD brains exhibit up to 50% of neuronal loss in the cortex, exceeding the number of NFTs (Gómez-Isla et al., 1997) PubMed:28420982

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

p(HBP:"paired helical filaments") partOf a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:

p(HGNC:SNAP25) negativeCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

In a prospective study three different synaptic protein (synaptophysin, SNAP-25 and syntaxin) were found to be progressively decreased in neocortex at Braak stages III-VI [158], NFT-bearing neurons demonstrating, for example, a 35%–57% reduction in synaptophysin mRNA in AD brain [159]. PubMed:26751493

Appears in Networks:

p(PFAM:Syntaxin) negativeCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

In a prospective study three different synaptic protein (synaptophysin, SNAP-25 and syntaxin) were found to be progressively decreased in neocortex at Braak stages III-VI [158], NFT-bearing neurons demonstrating, for example, a 35%–57% reduction in synaptophysin mRNA in AD brain [159]. PubMed:26751493

Appears in Networks:

r(HGNC:SYP) negativeCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

In a prospective study three different synaptic protein (synaptophysin, SNAP-25 and syntaxin) were found to be progressively decreased in neocortex at Braak stages III-VI [158], NFT-bearing neurons demonstrating, for example, a 35%–57% reduction in synaptophysin mRNA in AD brain [159]. PubMed:26751493

Appears in Networks:

path(MESH:"Alzheimer Disease") association a(GO:"neurofibrillary tangle") View Subject | View Object

AD (Alzheimer’s disease) is a progressive neurodegenerative disorder characterized by the extracellular accumulation of senile plaques composed of Aβ (amyloid β-peptide) and the intracellular accumulation of the MAP (microtubuleassociated protein) tau into both non-filamentous and filamentous inclusions, such as NFTs (neurofibrillary tangles), NTs (neuropil threads) and NPs (neuritic plaques) [1,2] PubMed:22817713

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Intracellular Space

act(a(CHEBI:acrolein)) positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

We were prompted to carry out this study because Acr is mainly localized in the neurons [54], is found in association with NFTs and dystrophic neurites surrounding senile plaques [55], is highly toxic to neurons, is found elevated 2–5 fold in affected regions of AD brain. EC can sequester highly reactive and toxic byproducts of oxidation such as acrolein. PubMed:23531502

Appears in Networks:

a(CHEBI:acrolein) increases a(GO:"neurofibrillary tangle") View Subject | View Object

Acrolein and methylglyoxal were the most reactive compounds followed by glyoxal and malondialdehyde in terms of formation of Tau dimers and higher molecular weight oligomers. Analysis of the Tau aggregates by electron microscopy study showed that formation of fibrils using wild-type Tau and several Tau mutants could be observed with acrolein and methylglyoxal but not with glyoxal and malondialdehyde. PubMed:17082178

Appears in Networks:

a(CHEBI:methylglyoxal) increases a(GO:"neurofibrillary tangle") View Subject | View Object

Acrolein and methylglyoxal were the most reactive compounds followed by glyoxal and malondialdehyde in terms of formation of Tau dimers and higher molecular weight oligomers. Analysis of the Tau aggregates by electron microscopy study showed that formation of fibrils using wild-type Tau and several Tau mutants could be observed with acrolein and methylglyoxal but not with glyoxal and malondialdehyde. PubMed:17082178

Appears in Networks:

a(HBP:pretangles) isA a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

E391-3610 mice (higher expressers) exhibit robust somatodendritic distribution of phospho- Ser 202/Thr 205 tau throughout the cortex, in hippocampal CA3 pyramidal neurons, CA1 apical dendrites and cell bodies and dentate granule cells. PubMed:22002427

Appears in Networks:
Annotations
Uberon
CA1 field of hippocampus
Uberon
CA3 field of hippocampus
Uberon
cerebral cortex
Uberon
dentate gyrus granule cell layer

p(HGNC:MAPT, pmod(Ph, Ser, 202)) partOf a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:

p(HGNC:TGM2) positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

Protein and mRNA levels of transglutaminase 1 were increased in globus pallidus of PSP as compared to controls. There were also significantly higher mRNA levels of the short form of transglutaminase 2 in globus pallidus of PSP (974% of control). Transglutaminase 1 mRNA and the long isoform of transglutaminase 2 mRNA (2212% of control) were significantly higher in PSP in the dentate of cerebellum. Together, these findings suggest that transglutaminase 1 and 2 enzymes may be involved in the formation and/or stabilization of neurofibrillary tangles in selectively vulnerable brain regions in PSP. These transglutaminases may be potential targets for therapeutic intervention. PubMed:12578227

Appears in Networks:

act(p(HGNC:TGM2)) positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

Total transglutaminase activity was significantly higher in the Alzheimer's disease prefrontal cortex compared to control. In addition the levels of tissue transglutaminase, as determined by quantitative immunoblotting, were elevated approximately 3-fold in Alzheimer's disease prefrontal cortex compared to control. To our knowledge, this is the first demonstration that transglutaminase is increased in Alzheimer's disease brain. There were no significant differences in transglutaminase activity or levels in the cerebellum between control and Alzheimer's disease cases. Because the elevation of transglutaminase in the Alzheimer's disease samples occurred in the prefrontal cortex, where neurofibrillary pathology is usually abundant, and not in the cerebellum, which is usually spared in Alzheimer's disease, it can be suggested that transglutaminase could be a contributing factor in neurofibrillary tangle formation. PubMed:9099822

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

complex(p(HGNC:MAPT), p(INTERPRO:"Triosephosphate isomerase", pmod(NO))) partOf a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:

act(p(ECCODE:"2.3.2.13")) positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

There were significantly higher levels of epsilon-(gamma-glutamyl) lysine cross-linking of PHF-tau in globus pallidus and pons regions of PSP cases compared to barely detectable cross-links in controls. The occipital cortex, an area spared from neurofibrillary pathology in PSP, showed no detectable cross-linking of PHF-tau protein in either PSP cases or control cases. Double-label immunofluorescence demonstrated the colocalization of the cross-link and PHF-tau in NFT in pons of PSP Previous studies and present data are consistent with the hypothesis that transglutaminase-induced cross-linking may be a factor contributing to the abnormal polymerization and stabilization of tau in straight and PHFs leading to neurofibrillary tangle formation in neurodegenerative diseases, including PSP and AD. PubMed:11089576

Appears in Networks:
Annotations
Uberon
globus pallidus
Uberon
pons

act(p(ECCODE:"2.3.2.13")) positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

The number of neurons that are immunoreactive with an antibody directed at the epsilon-(gamma-glutamyl)lysine bond was significantly higher in AD cortex compared with age-matched controls and schizophrenics. PHF tau-directed antibodies AT8, MC-1 and PHF-1 co-localized with epsilon(gamma-glutamyl)lysine immunolabeling in AD NFT. Immunoaffinity purification and immunoblotting experiments demonstrated that PHF tau contains epsilon(gamma-glutamyl)lysine bonds in parietal and frontal cortex in AD. In control cases with NFT present in the entorhinal cortex and hippocampus, indicative of Braak and Braak stage II, epsilon(gamma-glutamyl)lysine bonds were present in PHF tau in parietal and frontal cortex, despite the lack of microscopically detectable NFT or senile plaques in these cortical regions. The presence of PHF tau with epsilon(gamma-glutamyl)lysine bonds in brain regions devoid of NFT in stage II (but regions, which would be expected to contain NFT in stage III) suggests that these bonds occur early in the formation of NFT. PubMed:11738469

Appears in Networks:
Annotations
Uberon
frontal cortex
Uberon
parietal cortex
Disease Ontology (DO)
Alzheimer's disease

act(p(ECCODE:"2.3.2.13")) positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

Degenerating neurons from the AD hippocampus, compared to neurons from the normal aged hippocampus, exhibited increased immunoreactivity for TGase and demonstrated co-labeling for PHF1 and anti-TGase. Our results suggest that TGase may be associated with the neurofibrillary degeneration observed in AD, thereby implicating TGase as a potential factor in the pathogenesis of Alzheimer's disease. PubMed:8985134

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

p(HBP:"CDK5R1 p25") positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

The accumulation of p25 involves neurofibrillary tangle (NFT) formation via regulation of tau phosphorylation (Wen et al. 2007; Su and Tsai 2011) PubMed:26118667

Appears in Networks:

p(HBP:"KXGS motif") increases a(GO:"neurofibrillary tangle") View Subject | View Object

We demonstrate that elevated HDAC6 activity increases phosphorylation of tau at the 12E8 epitope (pS262/356), a phospho-epitope present within the KXGS motifs of tau’s microtubule-binding domain. The phosphorylation of KXGS motifs within tau by the kinase Par-1/MARK2 is required for tau proteotoxicity in Drosophila [29], observed at very early stages of NFT formation in AD brain [30], and appears to prime tau for subsequent phosphorylation events PubMed:25031639

Appears in Networks:

p(HBP:"Tau epitope, AT8") association a(GO:"neurofibrillary tangle") View Subject | View Object

The pSer422 antibody displayed an almost identical pattern to that of AT8, in that it stained NFTs (Figure 5A–D), neuropil threads and neuritic plaques (Figure 5E–H) PubMed:18239272

Appears in Networks:

p(HBP:"Tau epitope, PHF1") increases a(GO:"neurofibrillary tangle") View Subject | View Object

Finally, these data validate PHF-1 as an efficient marker for AD cytopathology following the progression of tau aggregation into NFT. PubMed:24033439

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:nitration, Tyr, 29)) partOf a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 205)) positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

E391-3610 mice (higher expressers) exhibit robust somatodendritic distribution of phospho- Ser 202/Thr 205 tau throughout the cortex, in hippocampal CA3 pyramidal neurons, CA1 apical dendrites and cell bodies and dentate granule cells. PubMed:22002427

Appears in Networks:
Annotations
Uberon
CA1 field of hippocampus
Uberon
CA3 field of hippocampus
Uberon
cerebral cortex
Uberon
dentate gyrus granule cell layer

p(HGNC:MAPT, pmod(Ph, Ser, 262)) partOf a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 422)) partOf a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Thr, 205)) partOf a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Asp13*")) partOf a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Asp25*")) partOf a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Asp368*")) partOf a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Asp421*")) partOf a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Glu391*")) partOf a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Glu391*")) partOf a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:

p(HGNC:TGM1) positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

Protein and mRNA levels of transglutaminase 1 were increased in globus pallidus of PSP as compared to controls. There were also significantly higher mRNA levels of the short form of transglutaminase 2 in globus pallidus of PSP (974% of control). Transglutaminase 1 mRNA and the long isoform of transglutaminase 2 mRNA (2212% of control) were significantly higher in PSP in the dentate of cerebellum. Together, these findings suggest that transglutaminase 1 and 2 enzymes may be involved in the formation and/or stabilization of neurofibrillary tangles in selectively vulnerable brain regions in PSP. These transglutaminases may be potential targets for therapeutic intervention. PubMed:12578227

Appears in Networks:

p(INTERPRO:"Syntaxin, N-terminal domain") negativeCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

In a prospective study three different synaptic protein (synaptophysin, SNAP-25 and syntaxin) were found to be progressively decreased in neocortex at Braak stages III-VI [158], NFT-bearing neurons demonstrating, for example, a 35%–57% reduction in synaptophysin mRNA in AD brain [159]. PubMed:26751493

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) increases a(GO:"neurofibrillary tangle") View Subject | View Object

Upon hyperphosphorylation, the protein Tau has a strong tendency to polymerize into neurofibrillary tangles in the brain, a hallmark of Alzheimer’s disease PubMed:19277525

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

p(FPLX:PPP2, pmod(Me, Tyr, 307)) association a(GO:"neurofibrillary tangle") View Subject | View Object

Lastly, increased phosphorylation of PP2A at Tyr-307 has been found in P-tau-rich, tangle-bearing neurons from post-mortem brain (Liu et al.,2008b). PubMed:24653673

Appears in Networks:
Annotations
MeSH
Neurons
MeSH
Alzheimer Disease

p(HGNC:BECN1, frag("?")) association a(GO:"neurofibrillary tangle") View Subject | View Object

For example, levels of Beclin 1, a key component of the class III type phosphoinositide 3-kinase/VPS34 complex essential to the pre-autophagosomal structure (PAS), has been suggested to be reduced in AD brains [16,17], with Rohn et al. demonstrating the cleavage of Beclin 1 by caspase-3 in the AD brain and colocalization of the cleaved product with NFTs [16]. PubMed:29758300

Appears in Networks:
Annotations
MeSH
Brain

a(HBP:"paired helical filaments") association a(GO:"neurofibrillary tangle") View Subject | View Object

Polyclonal antibodies to the classical paired helical filaments (PHFs) found in the neurofibrillary tangles and dystrophic neurites of AD were first raised in about 1982, allowing exploration of the component(s) of PHFs using immunochemical approaches (Ihara et al. 1983) PubMed:22908190

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(MESH:Ubiquitin) association a(GO:"neurofibrillary tangle") View Subject | View Object

In AD cortical sections, we observed that NFTs and dystrophic neurites (Fig. 1) and, unexpectedly, granulovacuolar changes (Fig. 1, inset) were intensely immunolabeled by the DF2 monoclonal. When mild fixation conditions were used, innumerable neuropil threads were also detected. PubMed:22908190

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Alzheimer Disease

bp(GO:"protein K63-linked ubiquitination") association a(GO:"neurofibrillary tangle") View Subject | View Object

For example, immunocytochemistry showing the presence of K63- linked polyubiquitin in a fraction of the NFTs in AD cortex (Paine et al. 2009) suggests an active involvement of autophagy in the mechanism of AD. PubMed:22908190

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(complex(GO:"proteasome complex")) negativeCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

That is, in areas where NFTs formed abundantly, including hippocampus and parahippocampal gyrus and superior and middle temporal gyri, proteasome activity (as assessed by chymortrypsinlike and postglutamyl peptidases) appeared to be most affected, whereas occipital gyri and cerebellum, which often have few or no NFTs, were least affected (Keller et al. 2000). PubMed:22908190

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Parahippocampal Gyrus
MeSH
Temporal Lobe

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) association a(GO:"neurofibrillary tangle") View Subject | View Object

Neurofibrillary tangles composed of tau proteins in a hyperphosphorylated state are rarely observed in abundance except in AD and a limited number of aging-related tauopathies. PubMed:22908190

Appears in Networks:

p(HGNC:UCHL1, pmod(GO:"protein oxidation")) negativeCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

A proteomic analysis has shown down-regulation and oxidative modification of UCH-L1 in the AD brain, and the levels of soluble UCH-L1 were inversely proportional to the number of NFTs (Choi et al. 2004). PubMed:22908190

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:SQSTM1) association a(GO:"neurofibrillary tangle") View Subject | View Object

p62 localizes to a variety of ubiquitin-positive neuropathological inclusions including Lewy bodies in Parkinson’s disease, neurofibrillary tangles in tauopathies, polyglutamine-expanded huntingtin aggregates in Huntington’s disease, and aggregates of mutant SOD1 in familial amyotrophic lateral sclerosis [85–87]. PubMed:18930136

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(HBP:"Tau aggregates") increases a(GO:"neurofibrillary tangle") View Subject | View Object

In the pathological case of Alzheimer’s disease (AD) tau becomes hyperphosphorylated, detaches from the microtubules, misfolds, and mislocalizes to the somatodendritic compartment where it aggregates into neurofibrillary tangles. PubMed:25374103

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:MAPT, frag("1_421")) increases a(GO:"neurofibrillary tangle") View Subject | View Object

In human AD brains and in the Tg4510 tauopathy mouse model, full-length tau is cleaved by caspase 3 behind Asp421 to generate tau1–421, which is prone to aggregation and subsequent formation of NFTs PubMed:26631930

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:MAPT, var("p.Lys280del")) increases a(GO:"neurofibrillary tangle") 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

Appears in Networks:

g(HGNC:"MIR9-1") decreases a(GO:"neurofibrillary tangle") View Subject | View Object

As regards, the MAPKK2 pathway, miR‐9 has been shown to inhibit tangles neurofibrillary by inhibiting this pathway and to play an important role in preventing AD. PubMed:30663117

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(p(HGNC:MAP2K2)) increases a(GO:"neurofibrillary tangle") View Subject | View Object

As regards, the MAPKK2 pathway, miR‐9 has been shown to inhibit tangles neurofibrillary by inhibiting this pathway and to play an important role in preventing AD. PubMed:30663117

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:MAPT, pmod(Ph)) increases a(GO:"neurofibrillary tangle") View Subject | View Object

By activating the CAMMK2 pathway, the β‐ameloid can aid in the phosphorylation of tau proteins and eventually trigger tangles neurofibrillary. PubMed:30663117

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(complex(GO:"NF-kappaB complex")) positiveCorrelation a(GO:"neurofibrillary tangle") View Subject | View Object

A consequence of intracellular and parenchymal accumulation of NPs and NFTs is activation of NF-κB in the neural and glial cells with subsequent protective or detrimental effects PubMed:25652642

Appears in Networks:
Annotations
MeSH
Neuroglia
MeSH
Neurons
MeSH
Alzheimer Disease

Out-Edges 61

a(GO:"neurofibrillary tangle") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

The histopathological changes in the brain include the presence of extracellular amyloid plaques consisted of various peptide variants of amyloid β (Aβ) and accumulation of intracellular neurofibrillary tangles (NFTs) composed mainly of phosphorylated Tau proteins (pTau), localized predominantly in neurons (reviewed by Serrano-Pozo et al. 2011). PubMed:29196815

Appears in Networks:
Annotations
Confidence
Medium

a(GO:"neurofibrillary tangle") positiveCorrelation p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) View Subject | View Object

MC-1–positive Tau accumulates in the axonal grains of proaggregant Tau as described above (arrowheads), whereas antiaggregant slices remain unstained PubMed:27671637

Appears in Networks:

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

Appears in Networks:
Annotations
Confidence
High

a(GO:"neurofibrillary tangle") increases bp(GO:"cell death") 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

Appears in Networks:
Annotations
Confidence
High

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

NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") positiveCorrelation p(MGI:Cdkn2a) View Subject | View Object

Cdkn2a transcript level, a hallmark measure of senescence, directly correlated with brain atrophy and NFT burden in mice PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases act(p(MGI:Cdkn2a)) View Subject | View Object

Consistent with NFTs from human AD, mouse NFTs also caused significant activation scores for IFNG, TNF, IL-1B, as well as enrichment in other senescence associated JAK, STAT, CDKN2A and BCL2 predicted upstream regulators (Figure 1c) indicating translational relevance for using tauNFT mice to explore our hypothesis PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases p(MGI:Cdkn2a) View Subject | View Object

Cdkn2a gene expression increased significantly during this age interval, and at 28 months of age tauWT Cdkn2a expression was similar to that of 16-month-old tauNFT mice (Figure 4c) PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases p(MGI:Cdkn2a) View Subject | View Object

In 15-month-old mice with heavy Abeta deposition and phosphorylated tau, but lacking NFT pathology (Orr et al., 2014), Cdkn2a expression was not elevated (Figure 4e). These data indicate that Cdkn2a expression was neither a response to general protein accumulation, nor to pre-NFT tau pathology, but instead required the presence of NFTs PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") association bp(GO:"cellular senescence") View Subject | View Object

Collectively, these findings indicate a strong association between the presence of NFTs and cellular senescence in the brain, which contributes to neurodegeneration PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Brain
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases bp(MESH:"Cell Survival") View Subject | View Object

NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases bp(GO:"inflammatory response") View Subject | View Object

NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases bp(GO:"cell cycle") View Subject | View Object

NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

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

NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") decreases path(MESH:Necrosis) View Subject | View Object

NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases p(HGNC:NFKB1) View Subject | View Object

NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases p(HGNC:IFNG) View Subject | View Object

NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases p(HGNC:TNF) View Subject | View Object

NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases p(HGNC:TLR4) View Subject | View Object

NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases p(HGNC:IL1B) View Subject | View Object

NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases p(HGNC:CXCL1) View Subject | View Object

NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases act(p(MGI:Ifng)) View Subject | View Object

Consistent with NFTs from human AD, mouse NFTs also caused significant activation scores for IFNG, TNF, IL-1B, as well as enrichment in other senescence associated JAK, STAT, CDKN2A and BCL2 predicted upstream regulators (Figure 1c) indicating translational relevance for using tauNFT mice to explore our hypothesis PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases act(p(MGI:Tnf)) View Subject | View Object

Consistent with NFTs from human AD, mouse NFTs also caused significant activation scores for IFNG, TNF, IL-1B, as well as enrichment in other senescence associated JAK, STAT, CDKN2A and BCL2 predicted upstream regulators (Figure 1c) indicating translational relevance for using tauNFT mice to explore our hypothesis PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases act(p(MGI:Il1b)) View Subject | View Object

Consistent with NFTs from human AD, mouse NFTs also caused significant activation scores for IFNG, TNF, IL-1B, as well as enrichment in other senescence associated JAK, STAT, CDKN2A and BCL2 predicted upstream regulators (Figure 1c) indicating translational relevance for using tauNFT mice to explore our hypothesis PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases act(p(MGI:Jak1)) View Subject | View Object

Consistent with NFTs from human AD, mouse NFTs also caused significant activation scores for IFNG, TNF, IL-1B, as well as enrichment in other senescence associated JAK, STAT, CDKN2A and BCL2 predicted upstream regulators (Figure 1c) indicating translational relevance for using tauNFT mice to explore our hypothesis PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases act(p(MGI:Stat1)) View Subject | View Object

Consistent with NFTs from human AD, mouse NFTs also caused significant activation scores for IFNG, TNF, IL-1B, as well as enrichment in other senescence associated JAK, STAT, CDKN2A and BCL2 predicted upstream regulators (Figure 1c) indicating translational relevance for using tauNFT mice to explore our hypothesis PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") increases act(p(MGI:Bcl2)) View Subject | View Object

Consistent with NFTs from human AD, mouse NFTs also caused significant activation scores for IFNG, TNF, IL-1B, as well as enrichment in other senescence associated JAK, STAT, CDKN2A and BCL2 predicted upstream regulators (Figure 1c) indicating translational relevance for using tauNFT mice to explore our hypothesis PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") association p(HGNC:CDKN2A) View Subject | View Object

Similarly, elevated expression of the cyclin dependent kinase inhibitor 2a, Cdkn2a, is one of the most robust markers of cellular senescence, and its protein product, p16INK4A, co-localizes with NFTs in human AD (Arendt et al., 1996) PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") positiveCorrelation p(HGNC:CDKN2A) View Subject | View Object

Consistent with the results from transgenic mice, CDKN2A was upregulated in PSP brains (P = 0.0415, Figure 4g) and expression correlated with NFT deposition, specifically in the parietal lobe (ANOVA, P = 0.0008; Kendall’s Tau rank correlation P = 0.059, Figure 4h) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Parietal Lobe
MeSH
Supranuclear Palsy, Progressive

a(GO:"neurofibrillary tangle") increases p(HGNC:CDKN2A) View Subject | View Object

Collectively, these findings led us to conclude that NFTs were directly linked to senescence-associated Cdkn2a upregulation, which in turn was a strong predictor of neurodegeneration and cognitive decline PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Parietal Lobe
MeSH
Supranuclear Palsy, Progressive

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

We found a significant genotype main effect for oxygen flux in both cortex and hippocampus, indicating that global respiratory capacity was impaired in NFT containing brain regions (P < 0.0001; Figure 3), an effect primarily driven by CI+CII respiration coupled to ATP production (cortex: P = 0.0034; hippocampus: P = 0.0215; Figure 2g and h, respectively), and uncoupled or maximum respiratory capacity (cortex: P = 0.0248; hippocampus: P = 0.0261; Figure 3g and h, respectively) PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") association path(MESH:"Hypertrophy, Right Ventricular") View Subject | View Object

NFTs are highly correlated with the rate of ventricular enlargement, an indicator of brain atrophy and hallmark of AD pathology (Silbert et al., 2003) PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

a(GO:"neurofibrillary tangle") association path(MESH:"Hypertrophy, Left Ventricular") View Subject | View Object

NFTs are highly correlated with the rate of ventricular enlargement, an indicator of brain atrophy and hallmark of AD pathology (Silbert et al., 2003) PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

a(GO:"neurofibrillary tangle") association path(HP:"Brain atrophy") View Subject | View Object

NFTs are highly correlated with the rate of ventricular enlargement, an indicator of brain atrophy and hallmark of AD pathology (Silbert et al., 2003) PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

a(GO:"neurofibrillary tangle") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Compared to non-demented controls, AD brains exhibit up to 50% of neuronal loss in the cortex, exceeding the number of NFTs (Gómez-Isla et al., 1997) PubMed:28420982

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

a(GO:"neurofibrillary tangle") negativeCorrelation r(HGNC:SYP) View Subject | View Object

In a prospective study three different synaptic protein (synaptophysin, SNAP-25 and syntaxin) were found to be progressively decreased in neocortex at Braak stages III-VI [158], NFT-bearing neurons demonstrating, for example, a 35%–57% reduction in synaptophysin mRNA in AD brain [159]. PubMed:26751493

Appears in Networks:

a(GO:"neurofibrillary tangle") negativeCorrelation p(HGNC:SNAP25) View Subject | View Object

In a prospective study three different synaptic protein (synaptophysin, SNAP-25 and syntaxin) were found to be progressively decreased in neocortex at Braak stages III-VI [158], NFT-bearing neurons demonstrating, for example, a 35%–57% reduction in synaptophysin mRNA in AD brain [159]. PubMed:26751493

Appears in Networks:

a(GO:"neurofibrillary tangle") negativeCorrelation p(PFAM:Syntaxin) View Subject | View Object

In a prospective study three different synaptic protein (synaptophysin, SNAP-25 and syntaxin) were found to be progressively decreased in neocortex at Braak stages III-VI [158], NFT-bearing neurons demonstrating, for example, a 35%–57% reduction in synaptophysin mRNA in AD brain [159]. PubMed:26751493

Appears in Networks:

a(GO:"neurofibrillary tangle") association path(MESH:"Alzheimer Disease") View Subject | View Object

AD (Alzheimer’s disease) is a progressive neurodegenerative disorder characterized by the extracellular accumulation of senile plaques composed of Aβ (amyloid β-peptide) and the intracellular accumulation of the MAP (microtubuleassociated protein) tau into both non-filamentous and filamentous inclusions, such as NFTs (neurofibrillary tangles), NTs (neuropil threads) and NPs (neuritic plaques) [1,2] PubMed:22817713

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Intracellular Space

a(GO:"neurofibrillary tangle") positiveCorrelation act(a(CHEBI:acrolein)) View Subject | View Object

We were prompted to carry out this study because Acr is mainly localized in the neurons [54], is found in association with NFTs and dystrophic neurites surrounding senile plaques [55], is highly toxic to neurons, is found elevated 2–5 fold in affected regions of AD brain. EC can sequester highly reactive and toxic byproducts of oxidation such as acrolein. PubMed:23531502

Appears in Networks:

a(GO:"neurofibrillary tangle") positiveCorrelation p(HGNC:TGM1) View Subject | View Object

Protein and mRNA levels of transglutaminase 1 were increased in globus pallidus of PSP as compared to controls. There were also significantly higher mRNA levels of the short form of transglutaminase 2 in globus pallidus of PSP (974% of control). Transglutaminase 1 mRNA and the long isoform of transglutaminase 2 mRNA (2212% of control) were significantly higher in PSP in the dentate of cerebellum. Together, these findings suggest that transglutaminase 1 and 2 enzymes may be involved in the formation and/or stabilization of neurofibrillary tangles in selectively vulnerable brain regions in PSP. These transglutaminases may be potential targets for therapeutic intervention. PubMed:12578227

Appears in Networks:

a(GO:"neurofibrillary tangle") positiveCorrelation p(HGNC:TGM2) View Subject | View Object

Protein and mRNA levels of transglutaminase 1 were increased in globus pallidus of PSP as compared to controls. There were also significantly higher mRNA levels of the short form of transglutaminase 2 in globus pallidus of PSP (974% of control). Transglutaminase 1 mRNA and the long isoform of transglutaminase 2 mRNA (2212% of control) were significantly higher in PSP in the dentate of cerebellum. Together, these findings suggest that transglutaminase 1 and 2 enzymes may be involved in the formation and/or stabilization of neurofibrillary tangles in selectively vulnerable brain regions in PSP. These transglutaminases may be potential targets for therapeutic intervention. PubMed:12578227

Appears in Networks:

a(GO:"neurofibrillary tangle") positiveCorrelation act(p(HGNC:TGM2)) View Subject | View Object

Total transglutaminase activity was significantly higher in the Alzheimer's disease prefrontal cortex compared to control. In addition the levels of tissue transglutaminase, as determined by quantitative immunoblotting, were elevated approximately 3-fold in Alzheimer's disease prefrontal cortex compared to control. To our knowledge, this is the first demonstration that transglutaminase is increased in Alzheimer's disease brain. There were no significant differences in transglutaminase activity or levels in the cerebellum between control and Alzheimer's disease cases. Because the elevation of transglutaminase in the Alzheimer's disease samples occurred in the prefrontal cortex, where neurofibrillary pathology is usually abundant, and not in the cerebellum, which is usually spared in Alzheimer's disease, it can be suggested that transglutaminase could be a contributing factor in neurofibrillary tangle formation. PubMed:9099822

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

a(GO:"neurofibrillary tangle") positiveCorrelation act(p(ECCODE:"2.3.2.13")) View Subject | View Object

There were significantly higher levels of epsilon-(gamma-glutamyl) lysine cross-linking of PHF-tau in globus pallidus and pons regions of PSP cases compared to barely detectable cross-links in controls. The occipital cortex, an area spared from neurofibrillary pathology in PSP, showed no detectable cross-linking of PHF-tau protein in either PSP cases or control cases. Double-label immunofluorescence demonstrated the colocalization of the cross-link and PHF-tau in NFT in pons of PSP Previous studies and present data are consistent with the hypothesis that transglutaminase-induced cross-linking may be a factor contributing to the abnormal polymerization and stabilization of tau in straight and PHFs leading to neurofibrillary tangle formation in neurodegenerative diseases, including PSP and AD. PubMed:11089576

Appears in Networks:
Annotations
Uberon
globus pallidus
Uberon
pons

a(GO:"neurofibrillary tangle") positiveCorrelation act(p(ECCODE:"2.3.2.13")) View Subject | View Object

The number of neurons that are immunoreactive with an antibody directed at the epsilon-(gamma-glutamyl)lysine bond was significantly higher in AD cortex compared with age-matched controls and schizophrenics. PHF tau-directed antibodies AT8, MC-1 and PHF-1 co-localized with epsilon(gamma-glutamyl)lysine immunolabeling in AD NFT. Immunoaffinity purification and immunoblotting experiments demonstrated that PHF tau contains epsilon(gamma-glutamyl)lysine bonds in parietal and frontal cortex in AD. In control cases with NFT present in the entorhinal cortex and hippocampus, indicative of Braak and Braak stage II, epsilon(gamma-glutamyl)lysine bonds were present in PHF tau in parietal and frontal cortex, despite the lack of microscopically detectable NFT or senile plaques in these cortical regions. The presence of PHF tau with epsilon(gamma-glutamyl)lysine bonds in brain regions devoid of NFT in stage II (but regions, which would be expected to contain NFT in stage III) suggests that these bonds occur early in the formation of NFT. PubMed:11738469

Appears in Networks:
Annotations
Uberon
frontal cortex
Uberon
parietal cortex
Disease Ontology (DO)
Alzheimer's disease

a(GO:"neurofibrillary tangle") positiveCorrelation act(p(ECCODE:"2.3.2.13")) View Subject | View Object

Degenerating neurons from the AD hippocampus, compared to neurons from the normal aged hippocampus, exhibited increased immunoreactivity for TGase and demonstrated co-labeling for PHF1 and anti-TGase. Our results suggest that TGase may be associated with the neurofibrillary degeneration observed in AD, thereby implicating TGase as a potential factor in the pathogenesis of Alzheimer's disease. PubMed:8985134

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

a(GO:"neurofibrillary tangle") association p(HBP:"Tau epitope, AT8") View Subject | View Object

The pSer422 antibody displayed an almost identical pattern to that of AT8, in that it stained NFTs (Figure 5A–D), neuropil threads and neuritic plaques (Figure 5E–H) PubMed:18239272

Appears in Networks:

a(GO:"neurofibrillary tangle") negativeCorrelation p(INTERPRO:"Syntaxin, N-terminal domain") View Subject | View Object

In a prospective study three different synaptic protein (synaptophysin, SNAP-25 and syntaxin) were found to be progressively decreased in neocortex at Braak stages III-VI [158], NFT-bearing neurons demonstrating, for example, a 35%–57% reduction in synaptophysin mRNA in AD brain [159]. PubMed:26751493

Appears in Networks:

a(GO:"neurofibrillary tangle") positiveCorrelation p(HBP:"CDK5R1 p25") View Subject | View Object

The accumulation of p25 involves neurofibrillary tangle (NFT) formation via regulation of tau phosphorylation (Wen et al. 2007; Su and Tsai 2011) PubMed:26118667

Appears in Networks:

a(GO:"neurofibrillary tangle") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

E391-3610 mice (higher expressers) exhibit robust somatodendritic distribution of phospho- Ser 202/Thr 205 tau throughout the cortex, in hippocampal CA3 pyramidal neurons, CA1 apical dendrites and cell bodies and dentate granule cells. PubMed:22002427

Appears in Networks:
Annotations
Uberon
CA1 field of hippocampus
Uberon
CA3 field of hippocampus
Uberon
cerebral cortex
Uberon
dentate gyrus granule cell layer

a(GO:"neurofibrillary tangle") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 205)) View Subject | View Object

E391-3610 mice (higher expressers) exhibit robust somatodendritic distribution of phospho- Ser 202/Thr 205 tau throughout the cortex, in hippocampal CA3 pyramidal neurons, CA1 apical dendrites and cell bodies and dentate granule cells. PubMed:22002427

Appears in Networks:
Annotations
Uberon
CA1 field of hippocampus
Uberon
CA3 field of hippocampus
Uberon
cerebral cortex
Uberon
dentate gyrus granule cell layer

a(GO:"neurofibrillary tangle") association p(FPLX:PPP2, pmod(Me, Tyr, 307)) View Subject | View Object

Lastly, increased phosphorylation of PP2A at Tyr-307 has been found in P-tau-rich, tangle-bearing neurons from post-mortem brain (Liu et al.,2008b). PubMed:24653673

Appears in Networks:
Annotations
MeSH
Neurons
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") association p(HGNC:BECN1, frag("?")) View Subject | View Object

For example, levels of Beclin 1, a key component of the class III type phosphoinositide 3-kinase/VPS34 complex essential to the pre-autophagosomal structure (PAS), has been suggested to be reduced in AD brains [16,17], with Rohn et al. demonstrating the cleavage of Beclin 1 by caspase-3 in the AD brain and colocalization of the cleaved product with NFTs [16]. PubMed:29758300

Appears in Networks:
Annotations
MeSH
Brain

a(GO:"neurofibrillary tangle") association a(HBP:"paired helical filaments") View Subject | View Object

Polyclonal antibodies to the classical paired helical filaments (PHFs) found in the neurofibrillary tangles and dystrophic neurites of AD were first raised in about 1982, allowing exploration of the component(s) of PHFs using immunochemical approaches (Ihara et al. 1983) PubMed:22908190

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") association a(MESH:Ubiquitin) View Subject | View Object

In AD cortical sections, we observed that NFTs and dystrophic neurites (Fig. 1) and, unexpectedly, granulovacuolar changes (Fig. 1, inset) were intensely immunolabeled by the DF2 monoclonal. When mild fixation conditions were used, innumerable neuropil threads were also detected. PubMed:22908190

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") negativeCorrelation act(complex(GO:"proteasome complex")) View Subject | View Object

That is, in areas where NFTs formed abundantly, including hippocampus and parahippocampal gyrus and superior and middle temporal gyri, proteasome activity (as assessed by chymortrypsinlike and postglutamyl peptidases) appeared to be most affected, whereas occipital gyri and cerebellum, which often have few or no NFTs, were least affected (Keller et al. 2000). PubMed:22908190

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Parahippocampal Gyrus
MeSH
Temporal Lobe

a(GO:"neurofibrillary tangle") negativeCorrelation p(HGNC:UCHL1, pmod(GO:"protein oxidation")) View Subject | View Object

A proteomic analysis has shown down-regulation and oxidative modification of UCH-L1 in the AD brain, and the levels of soluble UCH-L1 were inversely proportional to the number of NFTs (Choi et al. 2004). PubMed:22908190

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") association bp(GO:"protein K63-linked ubiquitination") View Subject | View Object

For example, immunocytochemistry showing the presence of K63- linked polyubiquitin in a fraction of the NFTs in AD cortex (Paine et al. 2009) suggests an active involvement of autophagy in the mechanism of AD. PubMed:22908190

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") association p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

Neurofibrillary tangles composed of tau proteins in a hyperphosphorylated state are rarely observed in abundance except in AD and a limited number of aging-related tauopathies. PubMed:22908190

Appears in Networks:

a(GO:"neurofibrillary tangle") association p(HGNC:SQSTM1) View Subject | View Object

p62 localizes to a variety of ubiquitin-positive neuropathological inclusions including Lewy bodies in Parkinson’s disease, neurofibrillary tangles in tauopathies, polyglutamine-expanded huntingtin aggregates in Huntington’s disease, and aggregates of mutant SOD1 in familial amyotrophic lateral sclerosis [85–87]. PubMed:18930136

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(GO:"neurofibrillary tangle") positiveCorrelation act(complex(GO:"NF-kappaB complex")) View Subject | View Object

A consequence of intracellular and parenchymal accumulation of NPs and NFTs is activation of NF-κB in the neural and glial cells with subsequent protective or detrimental effects PubMed:25652642

Appears in Networks:
Annotations
MeSH
Neuroglia
MeSH
Neurons
MeSH
Alzheimer Disease

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.