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

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

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

In-Edges 39

p(HGNC:MAPT) association a(GO:microtubule) View Subject | View Object

In contrast, the neurofibrillary tangles are intracellular and are rich in tau, a structural protein that is normally associated with microtubuli PubMed:14556719

p(HGNC:CDK5) association a(GO:microtubule) View Subject | View Object

Fig. 5 shows that the 31 kDa kinase is included in the MAP fraction after three or more cycles of microtubule assembly (lanes l-6), and is also associated with PHFs (lane 7) PubMed:8282104

p(FPLX:ERK) association a(GO:microtubule) View Subject | View Object

In this regard, cdk5 is similar to PKA [30], MAP kinase, and GSK-3 [12,17,26], but distinct from PKC or CaMK which do not copurify with microtubules [34] PubMed:8282104

p(FPLX:GSK3) association a(GO:microtubule) View Subject | View Object

In this regard, cdk5 is similar to PKA [30], MAP kinase, and GSK-3 [12,17,26], but distinct from PKC or CaMK which do not copurify with microtubules [34] PubMed:8282104

p(HGNC:PRKACA) association a(GO:microtubule) View Subject | View Object

In this regard, cdk5 is similar to PKA [30], MAP kinase, and GSK-3 [12,17,26], but distinct from PKC or CaMK which do not copurify with microtubules [34] PubMed:8282104

a(CHEBI:"epothilone A") increases a(GO:microtubule) View Subject | View Object

The microtubule stabilizers paclitaxel and epothilone A countered Aβ42-induced cytoskeletal disruption — and moderated excessive UPR — in neurons 182 . PubMed:30116051

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

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

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

The microtubule stabilizers paclitaxel and epothilone A countered Aβ42-induced cytoskeletal disruption — and moderated excessive UPR — in neurons 182 . PubMed:30116051

a(CHEBI:paclitaxel) increases a(GO:microtubule) View Subject | View Object

The microtubule stabilizers paclitaxel and epothilone A countered Aβ42-induced cytoskeletal disruption — and moderated excessive UPR — in neurons 182 . PubMed:30116051

a(HBP:"Tau oligomers") decreases act(a(GO:microtubule)) View Subject | View Object

In fact, tau oligomers might disrupt microtubule stability and trafficking, thus affecting organelle distribution PubMed:28420982

p(HGNC:MAPT) increases a(GO:microtubule) View Subject | View Object

While functional tau is an unfolded monomeric protein that stabilizes microtubules, regulates neurite growth, and monitors axonal transport of organelles (Medina and Avila, 2014), dysfunctional tau acquires a new toxic function PubMed:28420982

p(HGNC:MAPT) increases a(GO:microtubule) View Subject | View Object

Tau proteins, microtubule-associated proteins, take part in the formation of microtubules for the sake of maintaining the stability of microtubules PubMed:29626319

act(p(HGNC:HDAC6)) negativeCorrelation a(GO:microtubule) View Subject | View Object

Overexpressed tau was hyperphosphorylated and resulted in decreased MT density and greater fragmentation. Using genetic screen, a histone deacetylase 6 (HDAC6) null mutation rescued tau-induced MT defects in both muscles and neurons. Genetic and pharmacological inhibition of the tubulin-specific deacetylase activity of HDAC6 indicates that the rescue effect may be mediated by increased MT acetylation. PubMed:23487739

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) decreases a(GO:microtubule) View Subject | View Object

Overexpressed tau was hyperphosphorylated and resulted in decreased MT density and greater fragmentation. Using genetic screen, a histone deacetylase 6 (HDAC6) null mutation rescued tau-induced MT defects in both muscles and neurons. Genetic and pharmacological inhibition of the tubulin-specific deacetylase activity of HDAC6 indicates that the rescue effect may be mediated by increased MT acetylation. PubMed:23487739

Appears in Networks:

complex(p(HGNC:PPP2CA), p(HGNC:PPP2R1A), p(INTERPRO:"Protein phosphatase 2A regulatory subunit PR55")) regulates a(GO:microtubule) View Subject | View Object

Deregulation of PP2A/Bα alone also affects microtubule stability (Nunbhakdi-Craig et al., 2007) and neurite outgrowth (Sontag et al.,2010) in neuroblastoma cells PubMed:24653673

complex(p(HGNC:PPP2CB), p(HGNC:PPP2R1A), p(INTERPRO:"Protein phosphatase 2A regulatory subunit PR55")) regulates a(GO:microtubule) View Subject | View Object

Deregulation of PP2A/Bα alone also affects microtubule stability (Nunbhakdi-Craig et al., 2007) and neurite outgrowth (Sontag et al.,2010) in neuroblastoma cells PubMed:24653673

a(CHEBI:paclitaxel) increases a(GO:microtubule) 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

p(HBP:"Tau isoform D (383 aa)", var("p.Pro301Leu")) decreases a(GO:microtubule) View Subject | View Object

At the later stages, the mutant-tau lines showed microtubule loss and non-apoptotic neuronal death, paralleled by a complete loss of touch response (62). PubMed:29191965

p(HBP:"Tau isoform D (383 aa)", var("p.Arg406Trp")) decreases a(GO:microtubule) View Subject | View Object

At the later stages, the mutant-tau lines showed microtubule loss and non-apoptotic neuronal death, paralleled by a complete loss of touch response (62). PubMed:29191965

bp(GO:"anterograde axonal transport") decreases a(GO:microtubule) View Subject | View Object

This leads to accumulation of mitochondria in the cell body where they cluster near the microtubule center [6]. PubMed:25374103

p(HGNC:MAPT) regulates act(a(GO:microtubule)) View Subject | View Object

The tau-protein is a natively soluble protein that plays a key role in the dynamics of microtubules PubMed:25374103

tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(MESH:"Dendritic Spines")) negativeCorrelation a(GO:microtubule) View Subject | View Object

In cultured neurons, missorted dendritic tau may mediate toxicity that is induced by Aβ or other stressors by promoting the translocation of tubulin tyrosine ligase-like enzyme 6 (TTLL6) into dendrites, and the severing of microtubules by spastin PubMed:26631930

p(HGNC:MAP2) increases a(GO:microtubule) View Subject | View Object

Among various identified MAPs, microtubule-associated protein 2 (MAP2), which belongs to the MAP2/Tau family, is enriched in the brain and especially in dendrites, where it contributes to microtubule stabilization and overall dendritic architecture. PubMed:30061532

path(MESH:Schizophrenia) negativeCorrelation act(a(GO:microtubule)) View Subject | View Object

The biological implication behind an impairment of microtubule dynamics is confirmed in post-mortem schizophrenic brain samples, as well as in mouse models of schizophrenia, where mTOR-dependent autophagy dysfunction is accompanied by an altered gene expression and protein levels of the microtubule-associated protein 6 (MAP6) PubMed:30061532

Out-Edges 9

a(GO:microtubule) association p(HGNC:MAPT) View Subject | View Object

In contrast, the neurofibrillary tangles are intracellular and are rich in tau, a structural protein that is normally associated with microtubuli PubMed:14556719

a(GO:microtubule) association p(HGNC:PRKACA) View Subject | View Object

In this regard, cdk5 is similar to PKA [30], MAP kinase, and GSK-3 [12,17,26], but distinct from PKC or CaMK which do not copurify with microtubules [34] PubMed:8282104

a(GO:microtubule) association p(FPLX:ERK) View Subject | View Object

In this regard, cdk5 is similar to PKA [30], MAP kinase, and GSK-3 [12,17,26], but distinct from PKC or CaMK which do not copurify with microtubules [34] PubMed:8282104

a(GO:microtubule) association p(HGNC:CDK5) View Subject | View Object

Fig. 5 shows that the 31 kDa kinase is included in the MAP fraction after three or more cycles of microtubule assembly (lanes l-6), and is also associated with PHFs (lane 7) PubMed:8282104

a(GO:microtubule) association p(FPLX:GSK3) View Subject | View Object

In this regard, cdk5 is similar to PKA [30], MAP kinase, and GSK-3 [12,17,26], but distinct from PKC or CaMK which do not copurify with microtubules [34] PubMed:8282104

a(GO:microtubule) negativeCorrelation act(p(HGNC:HDAC6)) View Subject | View Object

Overexpressed tau was hyperphosphorylated and resulted in decreased MT density and greater fragmentation. Using genetic screen, a histone deacetylase 6 (HDAC6) null mutation rescued tau-induced MT defects in both muscles and neurons. Genetic and pharmacological inhibition of the tubulin-specific deacetylase activity of HDAC6 indicates that the rescue effect may be mediated by increased MT acetylation. PubMed:23487739

Appears in Networks:

a(GO:microtubule) increases bp(GO:"autophagosome-lysosome fusion") View Subject | View Object

Microtubule-based vesicular trafficking is essential for delivery of autophagosomes to lysosomes and subsequent fusion [46], and impaired dynein-mediated trafficking is associated with impaired autophagosome/ lysosome fusion and reduced protein turnover [47,48]. PubMed:18930136

a(GO:microtubule) negativeCorrelation tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(MESH:"Dendritic Spines")) View Subject | View Object

In cultured neurons, missorted dendritic tau may mediate toxicity that is induced by Aβ or other stressors by promoting the translocation of tubulin tyrosine ligase-like enzyme 6 (TTLL6) into dendrites, and the severing of microtubules by spastin PubMed:26631930

act(a(GO:microtubule)) negativeCorrelation path(MESH:Schizophrenia) View Subject | View Object

The biological implication behind an impairment of microtubule dynamics is confirmed in post-mortem schizophrenic brain samples, as well as in mouse models of schizophrenia, where mTOR-dependent autophagy dysfunction is accompanied by an altered gene expression and protein levels of the microtubule-associated protein 6 (MAP6) PubMed:30061532

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