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path(MESH:Tauopathies)

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Entity

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

Appears in Networks 20

Interplay of pathogenic forms of human tau with different autophagic pathways v1.0.1

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

Analysis of Isoform-specific Tau Aggregates Suggests a Common Toxic Mechanism Involving Similar Pathological Conformations and Axonal Transport Inhibition v1.0.1

Pathogenic forms of tau inhibit kinesin-dependent axonal transport through a mechanism involving activation of axonal phosphotransferases. v1.0.0

TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading 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

Neuropathogenic role of adenylate kinase-1 in Aβ-mediated tau phosphorylation via AMPK and GSK3β. v1.0.0

Tau Internalization is Regulated by 6-O Sulfation on Heparan Sulfate Proteoglycans (HSPGs) v1.0.1

Tau oligomers-Cytotoxicity, propagation, and mitochondrial damage v1.0.0

Tau oligomers-Cytotoxicity, propagation, and mitochondrial damage from Shafiei et al., 2017

Imbalances in the Hsp90 Chaperone Machinery: Implications for Tauopathies v1.0.0

Clearance of Amyloid Beta and Tau in Alzheimer’s Disease:from Mechanisms to Therapy v1.0.1

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

Pathological missorting of endogenous MAPT/Tau in neurons caused by failure of protein degradation systems v1.0.0

Caenorhabditis elegans models of tauopathy 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

Pathological missorting of endogenous MAPT/Tau in neurons caused by failure of protein degradation systems v1.0.1

In-Edges 54

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:

p(HGNC:NPEPPS) decreases path(MESH:Tauopathies) View Subject | View Object

In addition, a non-functional PSA mutant exacerbated tau pathology in a Drosophila model of tauopathy, while overexpressing PSA ameliorated the tau phenotype and diminished tau levels (10). Overexpressing PSA had a similar effect in the TAUP301L mice, reducing the pathologic phenotype (delaying paralysis, increasing motor neuron density in the spinal cord, decreasing gliosis) and decreasing tau levels (12). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

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

Given that in animal models of AD reducing tau levels attenuates neuronal dysfunction (7, 8), and in humans the extent of tau pathology correlates with cognitive decline (9), there is a growing interest in defining the degradative pathways that remove tau from the cell. PubMed:24027553

Appears in Networks:
Annotations
MeSH
Alzheimer Disease
Text Location
Review

a(HBP:"Tau oligomers") positiveCorrelation path(MESH:Tauopathies) View Subject | View Object

In general, the remarkable co-localization between TNT1, TOC1 and R1 in all tauopathies confirms that PAD exposure and tau oligomerization occur simultaneously in cells displaying tau pathology, irrespective of isoform composition PubMed:27574109

Appears in Networks:

a(HBP:"phosphatase-activating domain") positiveCorrelation path(MESH:Tauopathies) View Subject | View Object

In general, the remarkable co-localization between TNT1, TOC1 and R1 in all tauopathies confirms that PAD exposure and tau oligomerization occur simultaneously in cells displaying tau pathology, irrespective of isoform composition PubMed:27574109

Appears in Networks:

p(HBP:"AT8 tau", pmod(Ph)) association path(MESH:Tauopathies) View Subject | View Object

Soluble AT8 tau monomers inhibited anterograde FAT (Fig. 6 A, C), while retrograde trans- port was unaffected (Fig. 6 A, D). These data indicate that phos- phorylation of tau at the AT8 epitope, which is associated with hyperphosphorylation of tau in AD and other tauopathies, renders soluble monomeric tau capable of inhibiting antero- grade FAT. PubMed:21734277

Appears in Networks:

p(MGI:Tfeb) decreases path(MESH:Tauopathies) View Subject | View Object

Overall, these results show that astroglial TFEB overexpression reduces tau pathology and gliosis in the hippocampus of PS19 tauopathy mice. PubMed:30108137

Appears in Networks:
Annotations
Cell Ontology (CL)
astrocyte
MeSH
Hippocampus

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

Tauopathies are a family of neurodegenerative disorders characterized by the appearance of aggregates of the microtubule-associating protein, tau. PubMed:21882945

Appears in Networks:

bp(GO:"neuron death") positiveCorrelation 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:"cellular senescence") association path(MESH:Tauopathies) View Subject | View Object

Experimental data from various studies indicate that tau pathology may be associated with cellular senescence, a fundamental aging mechanism shown to contribute to several chronic diseases (recent review Kirkland and Tchkonia, 2017) PubMed:30126037

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

p(MGI:Mapt, var("p.Pro301Leu")) increases path(MESH:Tauopathies) 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(MESH:"Supranuclear Palsy, Progressive") association path(MESH:Tauopathies) 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(CHEBI:"amyloid-beta polypeptide 42") association path(MESH:Tauopathies) View Subject | View Object

A number of studies have found that Ab species, including oligomeric Ab42, are important factors responsible for tau pathogenesis PubMed:22419736

Appears in Networks:

a(HBP:"Tau oligomers") positiveCorrelation path(MESH:Tauopathies) View Subject | View Object

Tau protein can form multiple quaternary structures in solution, and recent evidence suggests that small tau oligomeric species may play a critical role in the spread of tau pathology and neurotoxicity PubMed:29686391

Appears in Networks:

a(HBP:"Tau annular protofibrils") association path(MESH:Tauopathies) View Subject | View Object

Hence, tau APFs may play a significant role in tauopathies by linking pore formation to cell death PubMed:28420982

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

a(HBP:"Tau oligomers") increases path(MESH:Tauopathies) View Subject | View Object

This indicates that tauopathies progress via a prion-like mechanism dependent upon tau oligomers (Gerson and Kayed, 2013; Castillo-Carranza et al., 2014b) PubMed:28420982

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex

a(HBP:"Tau oligomers") increases path(MESH:Tauopathies) View Subject | View Object

These studies demonstrate that tau oligomers may be the toxic entities responsible for neurodegeneration in tauopathies (Ward et al., 2012 PubMed:28420982

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Hippocampus

bp(GO:"neuron death") association path(MESH:Tauopathies) View Subject | View Object

In AD, tau pathology and neuronal cell loss coincide in the same brain regions, and as brain dysfunction progresses, NFTs are found in greater anatomical distributions (Ihara, 2001) PubMed:28420982

Appears in Networks:
Annotations
Confidence
High

complex(p(HGNC:CHRM1), p(HGNC:MAPT)) increases path(MESH:Tauopathies) View Subject | View Object

In other words, it is sensible to theorize that tauopathies progress via interaction of extracellular tau with M1 and M3 receptors on neurons leading to cytotoxic effects (Gómez-Ramos et al., 2009) PubMed:28420982

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

complex(p(HGNC:CHRM3), p(HGNC:MAPT)) increases path(MESH:Tauopathies) View Subject | View Object

In other words, it is sensible to theorize that tauopathies progress via interaction of extracellular tau with M1 and M3 receptors on neurons leading to cytotoxic effects (Gómez-Ramos et al., 2009) PubMed:28420982

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

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

The pathological accumulation of tau is a hallmark in several neurodegenerative disorders collectively termed tauopathies (Kovacs, 2015); a series of diseases including Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), Pick’s disease, and chronic traumatic encephalopathy (CTE; Guo et al., 2017). PubMed:29311797

Appears in Networks:

act(p(FPLX:HSP90), ma(GO:"ATPase activity")) increases path(MESH:Tauopathies) View Subject | View Object

Inhibition of the ATPase activity of Hsp90 has been shown to have positive outcomes in cell culture and animal models of tauopathy. PubMed:29311797

Appears in Networks:

p(HGNC:TOMM34) decreases path(MESH:Tauopathies) View Subject | View Object

One study found that in Drosophila, impaired Tom34 gene function led to enhanced tau pathology (Ambegaokar and Jackson, 2011). PubMed:29311797

Appears in Networks:
Annotations
MeSH
Cerebral Cortex

path(MESH:"Alzheimer Disease") isA path(MESH:Tauopathies) View Subject | View Object

Appears in Networks:

path(MESH:"Chronic Traumatic Encephalopathy") isA path(MESH:Tauopathies) View Subject | View Object

Appears in Networks:

path(MESH:"Pick Disease of the Brain") isA path(MESH:Tauopathies) View Subject | View Object

Appears in Networks:

path(MESH:"Supranuclear Palsy, Progressive") isA path(MESH:Tauopathies) View Subject | View Object

Appears in Networks:

a(CHEBI:"ginsenoside Rg1") decreases path(MESH:Tauopathies) View Subject | View Object

And ginsenoside Rg1 and granulocyte-colony stimulating factor may up-regulate activities of NEP in retinal cells in an AD mouse model to reduce tau protein pathology (He et al. 2014) (Doi et al.2014). PubMed:29626319

Appears in Networks:

a(MESH:"Granulocyte Colony-Stimulating Factor") decreases path(MESH:Tauopathies) View Subject | View Object

And ginsenoside Rg1 and granulocyte-colony stimulating factor may up-regulate activities of NEP in retinal cells in an AD mouse model to reduce tau protein pathology (He et al. 2014) (Doi et al.2014). PubMed:29626319

Appears in Networks:

complex(p(HGNC:PPP2CB), p(HGNC:PPP2R1A), p(INTERPRO:"Protein phosphatase 2A regulatory subunit PR55")) negativeCorrelation path(MESH:Tauopathies) View Subject | View Object

Notably, the loss of neuronal PP2A/Bα holoenzymes correlates with the down-regulation of PP2A methylation and severity of phosphorylated tau (P-tau) pathology in AD-affected brain regions (Sontag et al.,2004 a,b). PubMed:24653673

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:epothilone) decreases path(MESH:Tauopathies) 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

Appears in Networks:

bp(GO:"proteasome-mediated ubiquitin-dependent protein catabolic process") decreases path(MESH:Tauopathies) View Subject | View Object

For instance, phosphorylated insoluble tau proteins dampen 26S proteasome activity, while activation of the UPS attenuates tauopathy [27] PubMed:29758300

Appears in Networks:

p(HGNC:MAPT) association path(MESH:Tauopathies) View Subject | View Object

Dysregulation of tau proteins can produce a spectrum of neurodegenerative diseases or tauopathies characterized by dementia and tau deposition, including AD, frontotemporal dementia (FTD), Niemann- Pick disease, corticobasal degeneration (CBD), tangle-only dementia (TOD) and progressive supranuclear palsy (PSP). PubMed:29758300

Appears in Networks:

p(HGNC:BIN1) positiveCorrelation path(MESH:Tauopathies) View Subject | View Object

Higher expression of BIN1 has been reported in AD brains, and suppression of BIN1 reduces tau toxicity, suggesting BIN1 involvement in tau pathology, as well [104]. PubMed:29758300

Appears in Networks:

path(MESH:Dementia) association path(MESH:Tauopathies) View Subject | View Object

Dysregulation of tau proteins can produce a spectrum of neurodegenerative diseases or tauopathies characterized by dementia and tau deposition, including AD, frontotemporal dementia (FTD), Niemann- Pick disease, corticobasal degeneration (CBD), tangle-only dementia (TOD) and progressive supranuclear palsy (PSP). PubMed:29758300

Appears in Networks:

a(CHEBI:sirolimus) decreases path(MESH:Tauopathies) View Subject | View Object

Consistent with these findings, rapamycin induction of autophagy reduces tau pathology in the triple transgenic AD-mouse model (Caccamo et al. 2010), whereas in other models, autophagic–lysosomal dysfunction amplifies tau pathology and tau neurotoxicity (Hamano et al. 2008; Khurana et al. 2010). PubMed:22908190

Appears in Networks:

a(CHEBI:sirolimus) decreases path(MESH:Tauopathies) View Subject | View Object

Peripheral administration of rapamycin to strongly stimulate autophagy substantially reduces amyloid deposition and tau pathology in both APPand triple transgenic mouse models of AD pathology (Caccamo et al. 2010; Spilman et al. 2010; Tian et al. 2011) PubMed:22908190

Appears in Networks:

bp(GO:autophagy) decreases path(MESH:Tauopathies) View Subject | View Object

Consistent with these findings, rapamycin induction of autophagy reduces tau pathology in the triple transgenic AD-mouse model (Caccamo et al. 2010), whereas in other models, autophagic–lysosomal dysfunction amplifies tau pathology and tau neurotoxicity (Hamano et al. 2008; Khurana et al. 2010). PubMed:22908190

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) positiveCorrelation path(MESH:Tauopathies) View Subject | View Object

MAPT in AD and other tauopathies is hyperphosphorylated [29] and the hyperphosphorylation has been proposed to drive the missorting of MAPT. PubMed:30145931

Appears in Networks:

p(HGNC:CHRNA7) association path(MESH:Tauopathies) View Subject | View Object

Some of these enhancer genes are specific only to the tau-induced disease phenotype and include genes encoding proteins like WNT2 (111), TTBK2 (112), GSK-3b (113), TAOK1 (114, 115), CTSE (116) and CHRNA7 (117), have been implicated in tau-mediated pathology. PubMed:29191965

Appears in Networks:

composite(p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")), p(HGNC:DNMBP)) increases path(MESH:Tauopathies) View Subject | View Object

A study from the same group whereby the knockdown of dynamin binding protein (DNMBP/TUBA), a known interactor of UNC-34 (120), elevated the toxicity induced by TauV337M(80), lends further support to this notion PubMed:29191965

Appears in Networks:

composite(p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")), p(HGNC:GCH1)) causesNoChange path(MESH:Tauopathies) View Subject | View Object

Loss of function in other genes (cat-2, cat-4, tph-1) that also regulate the dopamine or serotonin levels (130–132),did not affect the tau-induced toxicity in TauV337M; however, their activity is essential for bas-1-mediated suppression of tau-induced toxicity in TauV337M (105) PubMed:29191965

Appears in Networks:

composite(p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")), p(HGNC:TH)) causesNoChange path(MESH:Tauopathies) View Subject | View Object

Loss of function in other genes (cat-2, cat-4, tph-1) that also regulate the dopamine or serotonin levels (130–132),did not affect the tau-induced toxicity in TauV337M; however, their activity is essential for bas-1-mediated suppression of tau-induced toxicity in TauV337M (105) PubMed:29191965

Appears in Networks:

composite(p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")), p(HGNC:TPH1)) causesNoChange path(MESH:Tauopathies) View Subject | View Object

Loss of function in other genes (cat-2, cat-4, tph-1) that also regulate the dopamine or serotonin levels (130–132),did not affect the tau-induced toxicity in TauV337M; however, their activity is essential for bas-1-mediated suppression of tau-induced toxicity in TauV337M (105) PubMed:29191965

Appears in Networks:

p(HGNC:ZC3H14) increases path(MESH:Tauopathies) View Subject | View Object

Homologs of SUT-2 exist in higher animals, including humans (MSUT-2), and reducing the MSUT-2 levels was found to be protective against tau-induced toxicity in a cell model (121). PubMed:29191965

Appears in Networks:

p(HGNC:CTSE) association path(MESH:Tauopathies) View Subject | View Object

Some of these enhancer genes are specific only to the tau-induced disease phenotype and include genes encoding proteins like WNT2 (111), TTBK2 (112), GSK-3b (113), TAOK1 (114, 115), CTSE (116) and CHRNA7 (117), have been implicated in tau-mediated pathology. PubMed:29191965

Appears in Networks:

p(HGNC:GSK3B) association path(MESH:Tauopathies) View Subject | View Object

Some of these enhancer genes are specific only to the tau-induced disease phenotype and include genes encoding proteins like WNT2 (111), TTBK2 (112), GSK-3b (113), TAOK1 (114, 115), CTSE (116) and CHRNA7 (117), have been implicated in tau-mediated pathology. PubMed:29191965

Appears in Networks:

p(HGNC:TAOK1) association path(MESH:Tauopathies) View Subject | View Object

Some of these enhancer genes are specific only to the tau-induced disease phenotype and include genes encoding proteins like WNT2 (111), TTBK2 (112), GSK-3b (113), TAOK1 (114, 115), CTSE (116) and CHRNA7 (117), have been implicated in tau-mediated pathology. PubMed:29191965

Appears in Networks:

p(HGNC:TTBK2) association path(MESH:Tauopathies) View Subject | View Object

Some of these enhancer genes are specific only to the tau-induced disease phenotype and include genes encoding proteins like WNT2 (111), TTBK2 (112), GSK-3b (113), TAOK1 (114, 115), CTSE (116) and CHRNA7 (117), have been implicated in tau-mediated pathology. PubMed:29191965

Appears in Networks:

p(HGNC:WNT2) association path(MESH:Tauopathies) View Subject | View Object

Some of these enhancer genes are specific only to the tau-induced disease phenotype and include genes encoding proteins like WNT2 (111), TTBK2 (112), GSK-3b (113), TAOK1 (114, 115), CTSE (116) and CHRNA7 (117), have been implicated in tau-mediated pathology. PubMed:29191965

Appears in Networks:

p(FPLX:Caspase) positiveCorrelation path(MESH:Tauopathies) View Subject | View Object

Recent data suggest that caspases are involved in the accumulation of tau pathology [10, 25, 26], and reductions in CHIP have been shown to cause caspase activation and increased caspase-cleaved tau levels [19]. PubMed:25374103

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:nitration, Tyr, 18)) positiveCorrelation path(MESH:Tauopathies) View Subject | View Object

The nitration of tau Tyr197 is found in the normal human brain and may have important physiological functions, whereas the nitration of Tyr18, Tyr29 and Tyr394 is detected only in AD or other tauopathies PubMed:26631930

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:nitration, Tyr, 29)) positiveCorrelation path(MESH:Tauopathies) View Subject | View Object

The nitration of tau Tyr197 is found in the normal human brain and may have important physiological functions, whereas the nitration of Tyr18, Tyr29 and Tyr394 is detected only in AD or other tauopathies PubMed:26631930

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:nitration, Tyr, 394)) positiveCorrelation path(MESH:Tauopathies) View Subject | View Object

The nitration of tau Tyr197 is found in the normal human brain and may have important physiological functions, whereas the nitration of Tyr18, Tyr29 and Tyr394 is detected only in AD or other tauopathies PubMed:26631930

Appears in Networks:

Out-Edges 33

path(MESH:Tauopathies) increases path(MESH:"Proteostasis Deficiencies") View Subject | View Object

Loss of neuronal proteostasis, a common feature of the aging brain, is accelerated in neurodegenerative disorders, including different types of tauopathies PubMed:29024336

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain
MeSH
Neurons

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

Given that in animal models of AD reducing tau levels attenuates neuronal dysfunction (7, 8), and in humans the extent of tau pathology correlates with cognitive decline (9), there is a growing interest in defining the degradative pathways that remove tau from the cell. PubMed:24027553

Appears in Networks:
Annotations
MeSH
Alzheimer Disease
Text Location
Review

path(MESH:Tauopathies) positiveCorrelation a(HBP:"Tau oligomers") View Subject | View Object

In general, the remarkable co-localization between TNT1, TOC1 and R1 in all tauopathies confirms that PAD exposure and tau oligomerization occur simultaneously in cells displaying tau pathology, irrespective of isoform composition PubMed:27574109

Appears in Networks:

path(MESH:Tauopathies) positiveCorrelation a(HBP:"phosphatase-activating domain") View Subject | View Object

In general, the remarkable co-localization between TNT1, TOC1 and R1 in all tauopathies confirms that PAD exposure and tau oligomerization occur simultaneously in cells displaying tau pathology, irrespective of isoform composition PubMed:27574109

Appears in Networks:

path(MESH:Tauopathies) association p(HBP:"AT8 tau", pmod(Ph)) View Subject | View Object

Soluble AT8 tau monomers inhibited anterograde FAT (Fig. 6 A, C), while retrograde trans- port was unaffected (Fig. 6 A, D). These data indicate that phos- phorylation of tau at the AT8 epitope, which is associated with hyperphosphorylation of tau in AD and other tauopathies, renders soluble monomeric tau capable of inhibiting antero- grade FAT. PubMed:21734277

Appears in Networks:

path(MESH:Tauopathies) increases p(MGI:Tfeb) View Subject | View Object

In the rTg4510 mouse model of tauopathy (Ramsden et al., 2005; SantaCruz et al., 2005), gene set enrichment analysis (GSEA) of microarray data revealed a similar enrichment of TFEB’s tran- scriptional profile when comparing 4-mo-old transgenic mice with widespread NFTs to wild-type mice, indicating TFEB’s activation with tau pathology (Fig. 1 F). PubMed:30108137

Appears in Networks:

path(MESH:Tauopathies) increases p(MGI:Tfeb) View Subject | View Object

Examining the protein levels in another tauopathy mouse model, hippocampal lysates from PS19 mice (Yoshiyama et al., 2007) at 10 mo of age showed increases in TFEB and lysosomal proteins LAMP1 and CTSD com- pared with wild-type mice (Fig. S1, G and H). PubMed:30108137

Appears in Networks:

path(MESH:Tauopathies) increases p(MGI:Lamp1) View Subject | View Object

Examining the protein levels in another tauopathy mouse model, hippocampal lysates from PS19 mice (Yoshiyama et al., 2007) at 10 mo of age showed increases in TFEB and lysosomal proteins LAMP1 and CTSD com- pared with wild-type mice (Fig. S1, G and H). PubMed:30108137

Appears in Networks:

path(MESH:Tauopathies) increases p(MGI:Ctsd) View Subject | View Object

Examining the protein levels in another tauopathy mouse model, hippocampal lysates from PS19 mice (Yoshiyama et al., 2007) at 10 mo of age showed increases in TFEB and lysosomal proteins LAMP1 and CTSD com- pared with wild-type mice (Fig. S1, G and H). PubMed:30108137

Appears in Networks:

path(MESH:Tauopathies) positiveCorrelation bp(GO:"neuron death") View Subject | View Object

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

Appears in Networks:

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

Appears in Networks:

path(MESH:Tauopathies) association bp(GO:"cellular senescence") View Subject | View Object

Experimental data from various studies indicate that tau pathology may be associated with cellular senescence, a fundamental aging mechanism shown to contribute to several chronic diseases (recent review Kirkland and Tchkonia, 2017) PubMed:30126037

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

path(MESH:Tauopathies) association path(MESH:"Supranuclear Palsy, Progressive") 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

path(MESH:Tauopathies) association a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

A number of studies have found that Ab species, including oligomeric Ab42, are important factors responsible for tau pathogenesis PubMed:22419736

Appears in Networks:

path(MESH:Tauopathies) positiveCorrelation a(HBP:"Tau oligomers") View Subject | View Object

Tau protein can form multiple quaternary structures in solution, and recent evidence suggests that small tau oligomeric species may play a critical role in the spread of tau pathology and neurotoxicity PubMed:29686391

Appears in Networks:

path(MESH:Tauopathies) association a(HBP:"Tau annular protofibrils") View Subject | View Object

Hence, tau APFs may play a significant role in tauopathies by linking pore formation to cell death PubMed:28420982

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

path(MESH:Tauopathies) association bp(GO:"neuron death") View Subject | View Object

In AD, tau pathology and neuronal cell loss coincide in the same brain regions, and as brain dysfunction progresses, NFTs are found in greater anatomical distributions (Ihara, 2001) PubMed:28420982

Appears in Networks:
Annotations
Confidence
High

path(MESH:Tauopathies) negativeCorrelation complex(p(HGNC:PPP2CB), p(HGNC:PPP2R1A), p(INTERPRO:"Protein phosphatase 2A regulatory subunit PR55")) View Subject | View Object

Notably, the loss of neuronal PP2A/Bα holoenzymes correlates with the down-regulation of PP2A methylation and severity of phosphorylated tau (P-tau) pathology in AD-affected brain regions (Sontag et al.,2004 a,b). PubMed:24653673

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

path(MESH:Tauopathies) association p(HGNC:MAPT) View Subject | View Object

Dysregulation of tau proteins can produce a spectrum of neurodegenerative diseases or tauopathies characterized by dementia and tau deposition, including AD, frontotemporal dementia (FTD), Niemann- Pick disease, corticobasal degeneration (CBD), tangle-only dementia (TOD) and progressive supranuclear palsy (PSP). PubMed:29758300

Appears in Networks:

path(MESH:Tauopathies) association path(MESH:Dementia) View Subject | View Object

Dysregulation of tau proteins can produce a spectrum of neurodegenerative diseases or tauopathies characterized by dementia and tau deposition, including AD, frontotemporal dementia (FTD), Niemann- Pick disease, corticobasal degeneration (CBD), tangle-only dementia (TOD) and progressive supranuclear palsy (PSP). PubMed:29758300

Appears in Networks:

path(MESH:Tauopathies) positiveCorrelation p(HGNC:BIN1) View Subject | View Object

Higher expression of BIN1 has been reported in AD brains, and suppression of BIN1 reduces tau toxicity, suggesting BIN1 involvement in tau pathology, as well [104]. PubMed:29758300

Appears in Networks:

path(MESH:Tauopathies) positiveCorrelation p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

MAPT in AD and other tauopathies is hyperphosphorylated [29] and the hyperphosphorylation has been proposed to drive the missorting of MAPT. PubMed:30145931

Appears in Networks:

path(MESH:Tauopathies) association p(HGNC:WNT2) View Subject | View Object

Some of these enhancer genes are specific only to the tau-induced disease phenotype and include genes encoding proteins like WNT2 (111), TTBK2 (112), GSK-3b (113), TAOK1 (114, 115), CTSE (116) and CHRNA7 (117), have been implicated in tau-mediated pathology. PubMed:29191965

Appears in Networks:

path(MESH:Tauopathies) association p(HGNC:TTBK2) View Subject | View Object

Some of these enhancer genes are specific only to the tau-induced disease phenotype and include genes encoding proteins like WNT2 (111), TTBK2 (112), GSK-3b (113), TAOK1 (114, 115), CTSE (116) and CHRNA7 (117), have been implicated in tau-mediated pathology. PubMed:29191965

Appears in Networks:

path(MESH:Tauopathies) association p(HGNC:GSK3B) View Subject | View Object

Some of these enhancer genes are specific only to the tau-induced disease phenotype and include genes encoding proteins like WNT2 (111), TTBK2 (112), GSK-3b (113), TAOK1 (114, 115), CTSE (116) and CHRNA7 (117), have been implicated in tau-mediated pathology. PubMed:29191965

Appears in Networks:

path(MESH:Tauopathies) association p(HGNC:TAOK1) View Subject | View Object

Some of these enhancer genes are specific only to the tau-induced disease phenotype and include genes encoding proteins like WNT2 (111), TTBK2 (112), GSK-3b (113), TAOK1 (114, 115), CTSE (116) and CHRNA7 (117), have been implicated in tau-mediated pathology. PubMed:29191965

Appears in Networks:

path(MESH:Tauopathies) association p(HGNC:CTSE) View Subject | View Object

Some of these enhancer genes are specific only to the tau-induced disease phenotype and include genes encoding proteins like WNT2 (111), TTBK2 (112), GSK-3b (113), TAOK1 (114, 115), CTSE (116) and CHRNA7 (117), have been implicated in tau-mediated pathology. PubMed:29191965

Appears in Networks:

path(MESH:Tauopathies) association p(HGNC:CHRNA7) View Subject | View Object

Some of these enhancer genes are specific only to the tau-induced disease phenotype and include genes encoding proteins like WNT2 (111), TTBK2 (112), GSK-3b (113), TAOK1 (114, 115), CTSE (116) and CHRNA7 (117), have been implicated in tau-mediated pathology. PubMed:29191965

Appears in Networks:

path(MESH:Tauopathies) positiveCorrelation p(FPLX:Caspase) View Subject | View Object

Recent data suggest that caspases are involved in the accumulation of tau pathology [10, 25, 26], and reductions in CHIP have been shown to cause caspase activation and increased caspase-cleaved tau levels [19]. PubMed:25374103

Appears in Networks:

path(MESH:Tauopathies) positiveCorrelation p(HGNC:MAPT, pmod(HBP:nitration, Tyr, 18)) View Subject | View Object

The nitration of tau Tyr197 is found in the normal human brain and may have important physiological functions, whereas the nitration of Tyr18, Tyr29 and Tyr394 is detected only in AD or other tauopathies PubMed:26631930

Appears in Networks:

path(MESH:Tauopathies) positiveCorrelation p(HGNC:MAPT, pmod(HBP:nitration, Tyr, 29)) View Subject | View Object

The nitration of tau Tyr197 is found in the normal human brain and may have important physiological functions, whereas the nitration of Tyr18, Tyr29 and Tyr394 is detected only in AD or other tauopathies PubMed:26631930

Appears in Networks:

path(MESH:Tauopathies) positiveCorrelation p(HGNC:MAPT, pmod(HBP:nitration, Tyr, 394)) View Subject | View Object

The nitration of tau Tyr197 is found in the normal human brain and may have important physiological functions, whereas the nitration of Tyr18, Tyr29 and Tyr394 is detected only in AD or other tauopathies PubMed:26631930

Appears in Networks:

path(MESH:Tauopathies) increases p(HGNC:MAPT, frag("?")) View Subject | View Object

The truncation of tau occurs in AD and in other tauopathies PubMed:26631930

Appears in Networks:

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.