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  3. PubMed:26631930

PubMed: 26631930

Title
Tau in physiology and pathology.
Journal
Nature reviews. Neuroscience
Volume
17
Issue
None
Pages
5-21
Date
2016-01-01
Authors
Mandelkow E | Wang Y

Evidence 49ee9a57ab
JSON

In addition, the aggregates may occupy space in the cell and thus directly interfere with axonal transport, leading to neurodegeneration

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

Appears in Networks:

bp(GO:"axonal transport") decreases path(HBP:Neurodegeneration) View Subject | View Object

Appears in Networks:

a(HBP:"Tau aggregates") decreases bp(GO:"axonal transport") View Subject | View Object

Appears in Networks:

Evidence 283fa5e918
JSON

This fragment was proposed to be generated by caspases (although not caspase 3).

p(FPLX:Caspase) increases p(HGNC:MAPT, frag("26_230")) View Subject | View Object

Appears in Networks:

Evidence 31ebebf08b
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However, tau aggregates are also observed in the brains of some aged individuals with a condition known as primary age-related tauopathy (PART)

a(HBP:"Tau aggregates") positiveCorrelation bp(GO:aging) View Subject | View Object

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Annotations
MeSH
Brain

bp(GO:aging) positiveCorrelation a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence d0d42bc172
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Tau aggregation decreases levels of soluble functional tau, which may result in microtubule disassembly as well

a(HBP:"Tau aggregates") decreases bp(GO:"microtubule polymerization") View Subject | View Object

Appears in Networks:

Evidence fb96895bd7
JSON

In the longer term, however, these tau aggregates may sequester other cell components, finally compromising neuronal functions

a(HBP:"Tau aggregates") decreases act(a(MESH:Neurons)) View Subject | View Object

Appears in Networks:

Evidence f5806bdefd
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The interaction of tau with FYN may regulate the postsynaptic targeting of FYN, and thereby mediate Aβ‑induced excitotoxicity

p(HGNC:MAPT) directlyIncreases complex(p(HGNC:FYN), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

complex(p(HGNC:FYN), p(HGNC:MAPT)) regulates path(HBP:Excitotoxicity) View Subject | View Object

Appears in Networks:

a(CHEBI:"amyloid-beta") increases path(HBP:Excitotoxicity) View Subject | View Object

Appears in Networks:

Evidence 023530228d
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Genetic deficiency of tau protects against excitotoxicity caused by Aβ or other excitotoxins in mice that overexpress human amyloid precursor protein (APP), in mice that express human APP and human presenilin 1 (PS1), and in mice that express mutant Scn1a (the gene encoding the voltage-gated sodium channel subunit Nav1.1), as well as in mice lacking the voltage-gated potassium channel Kv1.1 subunit

a(CHEBI:"amyloid-beta") increases path(HBP:Excitotoxicity) View Subject | View Object

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p(HGNC:MAPT) increases path(HBP:Excitotoxicity) View Subject | View Object

Appears in Networks:

Evidence 783de9e02b
JSON

Tau aggregation could be accelerated by cofactors such as polyanions that compensate for the repulsive positive charges of tau

a(CHEBI:"polyanionic polymer") increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence 3bd4cc74d3
JSON

Conversely, tau aggregation can be induced in vitro efficiently by polyanionic cofactors, regardless of phosphorylation

a(CHEBI:"polyanionic polymer") increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence f65ef3f56a
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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

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

Appears in Networks:

tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(MESH:"Dendritic Spines")) regulates act(a(CHEBI:"amyloid-beta")) View Subject | View Object

Appears in Networks:

tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(MESH:"Dendritic Spines")) increases tloc(p(HGNC:TTLL6), fromLoc(GO:axon), toLoc(MESH:"Dendritic Spines")) View Subject | View Object

Appears in Networks:

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

Appears in Networks:

p(HGNC:SPAST) increases bp(GO:"microtubule severing") View Subject | View Object

Appears in Networks:

tloc(p(HGNC:TTLL6), fromLoc(GO:axon), toLoc(MESH:"Dendritic Spines")) increases act(a(CHEBI:"amyloid-beta")) View Subject | View Object

Appears in Networks:

Evidence d4bfde45d0
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To date, the physiological function of dendritic tau has not been well characterized. It may be involved in the regulation of synaptic plasticity, as pharmacological synaptic activation induces translocation of endogenous tau from the dendritic shaft to excitatory postsynaptic compartments in cultured mouse neurons and in acute hippocampal slices

act(a(GO:synapse)) increases tloc(p(HGNC:MAPT), fromLoc(GO:"dendritic shaft"), toLoc(GO:"excitatory synapse")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dendritic Spines

bp(GO:"regulation of synaptic plasticity") association p(HGNC:MAPT) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dendritic Spines

p(HGNC:MAPT) association bp(GO:"regulation of synaptic plasticity") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dendritic Spines

Evidence 877665b9a4
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Hyperphosphorylation, mutations and overexpression of tau can drive the mislocalization of tau into postsynaptic spines, resulting in synaptic dysfunction

act(a(GO:synapse)) negativeCorrelation p(HGNC:MAPT) View Subject | View Object

Appears in Networks:

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

Appears in Networks:

p(HGNC:MAPT) negativeCorrelation act(a(GO:synapse)) View Subject | View Object

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) increases tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(MESH:"Dendritic Spines")) View Subject | View Object

Appears in Networks:

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

Appears in Networks:

p(HGNC:MAPT, var("?")) increases tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(MESH:"Dendritic Spines")) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("?")) decreases act(a(GO:synapse)) View Subject | View Object

Appears in Networks:

Evidence 7e46ce4717
JSON

Third, the phosphorylation of tau is often considered to enhance tau aggregation, as hyperphosphorylation and aggregation are both increased in AD

a(HBP:"Tau aggregates") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

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

Appears in Networks:

p(HGNC:MAPT, pmod(Ph)) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

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

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence 5483a09e92
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This suggests that the stabilization of the microtubule-bound conformation of tau may delay tau aggregation

a(HBP:"Tau aggregates") negativeCorrelation complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

complex(a(GO:microtubule), p(HGNC:MAPT)) negativeCorrelation a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence 8a94382271
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In an analogy to the evolution of concepts in the ‘amyloid cascade hypothesis’, which proposes that soluble oligomers — rather than insoluble aggregates of amyloid peptides — are the causative agents of neurodegeneration in AD, recent studies have suggested tau oligomers to be the toxic species, and indeed levels of SDS-stable tau oligomers are increased in AD and PSP brains.

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

Appears in Networks:
Annotations
MeSH
Brain

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

Appears in Networks:
Annotations
MeSH
Brain

a(HBP:"Tau oligomers") positiveCorrelation path(MESH:"Supranuclear Palsy, Progressive") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

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

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:"Supranuclear Palsy, Progressive") positiveCorrelation a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence f07f5b8197
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Some studies showed in cell toxicity assays that tau oligomers made from pro-aggregant recombinant tau were toxic to cultured cells; other studies in cultured neurons found that oligomers induced only local neurotoxicity that led to loss of spines

a(HBP:"Tau oligomers") decreases a(MESH:"Dendritic Spines") View Subject | View Object

Appears in Networks:

Evidence d7d1f19dd7
JSON

The phosphorylation of tau at Tyr394 and Tyr18 is present in PHFs in the brains of individuals with AD.

p(HGNC:MAPT, pmod(Ph, Tyr, 394)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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p(HGNC:MAPT, pmod(Ph, Tyr, 394)) association a(HBP:"paired helical filaments") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Tyr, 394)) View Subject | View Object

Appears in Networks:

a(HBP:"paired helical filaments") association p(HGNC:MAPT, pmod(Ph, Tyr, 18)) View Subject | View Object

Appears in Networks:

a(HBP:"paired helical filaments") association p(HGNC:MAPT, pmod(Ph, Tyr, 394)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Tyr, 18)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Tyr, 18)) association a(HBP:"paired helical filaments") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Tyr, 18)) View Subject | View Object

Appears in Networks:

Evidence 70b8759016
JSON

It can do this by influencing the function of the motor proteins dynein and kinesin, which transport cargoes towards the minus ends (towards the cell body) and plus ends of microtubules (towards the axonal terminus), respectively (FIG. 3).

act(a(MESH:Dyneins)) association p(HGNC:MAPT) View Subject | View Object

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act(a(MESH:Kinesin)) association p(HGNC:MAPT) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT) association act(a(MESH:Dyneins)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT) association act(a(MESH:Kinesin)) View Subject | View Object

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p(HGNC:MAPT) regulates bp(GO:"axonal transport") View Subject | View Object

Appears in Networks:

Evidence 3981a2ccc5
JSON

Finally, inhibition of mitochondrial complex I (for example, using annonacin or MPP+ (1‑methyl‑4‑phenylpyridinium)) upregulates expression of the splicing factor SRSF2, thus promoting expression of 4R tau in human neurons.

a(PUBCHEM:354398) decreases act(complex(GO:"mitochondrial respiratory chain complex I")) View Subject | View Object

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complex(GO:"mitochondrial respiratory chain complex I") decreases p(HGNC:SRSF2) View Subject | View Object

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p(HGNC:SRSF2) increases p(HBP:"4R tau") View Subject | View Object

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Evidence 640951edbb
JSON

In brains of individuals with AD, neuron loss in the superior temporal sulcus region exceeds the number of NFTs more than sevenfold, implying that the majority of neurons probably die without having developed NFTs

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

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

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Evidence be7079ff9f
JSON

Tau phosphorylated at Ser262 or Ser356 cannot be recognized by the C terminus of HSP70‑interacting protein–heat shock protein 90 (CHIP–HSP90) complex and is thus spared from proteasomal degradation

bp(GO:"proteasomal protein catabolic process") increases deg(p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

bp(GO:"proteasomal protein catabolic process") decreases deg(p(HGNC:MAPT, pmod(Ph, Ser, 262), pmod(Ph, Ser, 356))) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 262), pmod(Ph, Ser, 356)) decreases complex(p(HGNC:MAPT), p(HGNC:STUB1)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 262), pmod(Ph, Ser, 356)) decreases deg(p(HGNC:MAPT, pmod(Ph, Ser, 262), pmod(Ph, Ser, 356))) View Subject | View Object

Appears in Networks:

Evidence b925089c0a
JSON

Tau is known to be ubiquitylated through Lys48 linkages by CHIP for proteasomal degradation

bp(GO:"proteasomal protein catabolic process") increases deg(p(HGNC:MAPT, pmod(Ub))) View Subject | View Object

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p(HGNC:STUB1) increases p(HGNC:MAPT, pmod(UbK48)) View Subject | View Object

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Evidence 574f9765c3
JSON

Notably, one study demonstrated that tau can also be ubiquitylated through Lys63 linkages by TNF receptor-associated factor 6 (TRAF6) — again, for proteasomal degradation

bp(GO:"proteasomal protein catabolic process") increases deg(p(HGNC:MAPT, pmod(UbK63))) View Subject | View Object

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p(HGNC:TRAF6) increases p(HGNC:MAPT, pmod(UbK63)) View Subject | View Object

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Evidence 9b8c65aa18
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It is not clear whether the discrepancy between these results is due to the differences between the knockout mouse lines; nevertheless, both papers point to some involvement of tau in neurogenesis

bp(GO:neurogenesis) association p(HGNC:MAPT) View Subject | View Object

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p(HGNC:MAPT) association bp(GO:neurogenesis) View Subject | View Object

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Evidence fa51443171
JSON

For example, hyperphosphorylated tau but not unphosphorylated tau can interact with the kinesin-associated protein JUN N‑terminal kinase-interacting protein 1 (JIP1) and thus impair the formation of the kinesin complex,which mediates axonal transport

complex(GO:"kinesin complex") regulates bp(GO:"axonal transport") View Subject | View Object

Appears in Networks:

complex(p(HGNC:MAPK8IP1), p(HGNC:MAPT, pmod(HBP:hyperphosphorylation))) decreases complex(GO:"kinesin complex") View Subject | View Object

Appears in Networks:

complex(p(HGNC:MAPK8IP1), p(HGNC:MAPT, pmod(HBP:hyperphosphorylation))) decreases bp(GO:"axonal transport") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) increases complex(p(HGNC:MAPK8IP1), p(HGNC:MAPT, pmod(HBP:hyperphosphorylation))) View Subject | View Object

Appears in Networks:

Evidence 9461ee525a
JSON

Third, some evidence suggests that expression of tau mRNA-binding proteins (such as RAS GTPase-activating protein-binding protein 1 and minor histocompatibility antigen H13) promotes the formation of ribonucleoprotein granules, resulting in a shift towards the expression of larger tau isoforms (such as high-molecular-weight tau and E3‑containing tau isoforms).

complex(GO:"ribonucleoprotein granule") increases p(HGNC:MAPT) View Subject | View Object

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p(HGNC:G3BP1) increases complex(GO:"ribonucleoprotein granule") View Subject | View Object

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p(HGNC:HM13) increases complex(GO:"ribonucleoprotein granule") View Subject | View Object

Appears in Networks:

Evidence f7b48fc3d0
JSON

Owing to the additional repeat domain R2, 4R tau shows higher affinity for microtubules than does 3R tau, and is therefore more efficient at promoting microtubule assembly

complex(a(GO:microtubule), p(HBP:"3R tau")) increases bp(GO:"microtubule polymerization") View Subject | View Object

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p(HBP:"3R tau") directlyIncreases complex(a(GO:microtubule), p(HBP:"3R tau")) View Subject | View Object

Appears in Networks:

complex(a(GO:microtubule), p(HBP:"4R tau")) increases bp(GO:"microtubule polymerization") View Subject | View Object

Appears in Networks:

p(HBP:"4R tau") directlyIncreases complex(a(GO:microtubule), p(HBP:"4R tau")) View Subject | View Object

Appears in Networks:

Evidence 5ea554cb98
JSON

Tauopathies can be classified into three groups on the basis of the tau isoforms found in the aggregates: 4R tauopathies (including PSP, CBD and AGD), 3R tauopathies (for example, PiD) and 3R+4R tauopathies (for example, AD)

p(HBP:"3R tau") positiveCorrelation path(MESH:"Niemann-Pick Diseases") View Subject | View Object

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p(HBP:"3R tau") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

p(HBP:"4R tau") positiveCorrelation path(MESH:"Supranuclear Palsy, Progressive") View Subject | View Object

Appears in Networks:

p(HBP:"4R tau") positiveCorrelation path(HBP:"Corticobasal Degeneration") View Subject | View Object

Appears in Networks:

p(HBP:"4R tau") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

path(HBP:"Corticobasal Degeneration") positiveCorrelation p(HBP:"4R tau") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation p(HBP:"4R tau") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation p(HBP:"3R tau") View Subject | View Object

Appears in Networks:

path(MESH:"Niemann-Pick Diseases") positiveCorrelation p(HBP:"3R tau") View Subject | View Object

Appears in Networks:

path(MESH:"Supranuclear Palsy, Progressive") positiveCorrelation p(HBP:"4R tau") View Subject | View Object

Appears in Networks:

Evidence 998f43257e
JSON

Fifth, tau may bind to the p150 subunit of dynactin and thereby facilitate the association of dynactin with microtubules, which stabilizes the interaction of dynein with microtubules and thus supports transport by dynein

complex(a(GO:microtubule), p(HGNC:DCTN1)) increases complex(a(GO:microtubule), a(MESH:Dyneins)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT) directlyIncreases complex(p(HGNC:DCTN1), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

complex(p(HGNC:DCTN1), p(HGNC:MAPT)) increases complex(a(GO:microtubule), p(HGNC:DCTN1)) View Subject | View Object

Appears in Networks:

Evidence d9705bc890
JSON

Tau thereby stabilizes microtubules, promotes microtubule assembly and, in particular, regulates the dynamic instability of microtubules that allows reorganization of the cytoskeleton.

complex(a(GO:microtubule), p(HGNC:MAPT)) increases bp(GO:"microtubule bundle formation") View Subject | View Object

Appears in Networks:

complex(a(GO:microtubule), p(HGNC:MAPT)) increases bp(GO:"actin cytoskeleton reorganization") View Subject | View Object

Appears in Networks:

Evidence 5db4433848
JSON

Thus, it is possible that unknown cofactors trigger tau aggregation in the AD brain, whereas phosphorylation may accelerate aggregation indirectly: for example, by detaching tau from microtubules

complex(a(GO:microtubule), p(HGNC:MAPT)) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:MAPT, pmod(Ph)) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

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

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

Evidence 139067a53e
JSON

Notably, tau has intrinsic acetyltransferase activity and so can catalyse auto-acetylation at certain Lys sites, including Lys280

p(HGNC:MAPT) directlyIncreases p(HGNC:MAPT, pmod(Ac, Lys, 280)) View Subject | View Object

Appears in Networks:

Evidence b765a5c5d9
JSON

First, hyperphosphorylation of tau might induce tau missorting from axons to the somatodendritic compartment, which can cause synaptic dysfunction

tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(GO:"somatodendritic compartment")) decreases act(a(GO:synapse)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) increases tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(GO:"somatodendritic compartment")) View Subject | View Object

Appears in Networks:

Evidence ce00749913
JSON

In human AD brains, the missorting of tau into dendrites represents one of the early signs of neurodegeneration

tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(MESH:"Dendritic Spines")) association path(HBP:Neurodegeneration) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

path(HBP:Neurodegeneration) association tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(MESH:"Dendritic Spines")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

path(MESH:"Alzheimer Disease") increases tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(MESH:"Dendritic Spines")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Evidence 38f49f7403
JSON

In addition, as tau is involved in multiple novel functions, including iron transport, neurogenesis, LTD and neuronal DNA protection (as discussed above), the loss of function of tau may also lead to neurodegeneration via impairment of these processes.

act(p(HGNC:MAPT)) decreases path(HBP:Neurodegeneration) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT) increases bp(GO:neurogenesis) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT) increases bp(GO:"long-term synaptic depression") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT) increases bp(GO:"iron ion transport") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT) increases bp(GO:"DNA protection") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

Evidence 467532ffaf
JSON

In adult neurons, tau mainly distributes into axons, where it interacts with microtubules through the repeat-domain and flanking regions.

p(HGNC:MAPT) directlyIncreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Axons

Evidence c442efd649
JSON

First, tau competes with kinesin or dynein motors for binding to microtubules, reducing the binding frequency, motile fraction and run length of kinesin and dynein (without changing the motor velocity of kinesin and dynein), and thereby slowing down both anterograde and retrograde transport

p(HGNC:MAPT) decreases complex(a(GO:microtubule), a(MESH:Dyneins)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT) decreases complex(a(GO:microtubule), a(MESH:Kinesin)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT) decreases bp(GO:"anterograde axonal transport") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT) decreases bp(GO:"retrograde axonal transport") View Subject | View Object

Appears in Networks:

Evidence 8a7c86cdea
JSON

Fourth, tau can regulate the release of cargo vesicles from kinesin chains by activating PP1 and glycogen synthase kinase 3β (GSK3β) via the 18 residues at the N terminus of tau

p(HGNC:MAPT) increases act(p(HGNC:GSK3B)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT) increases act(p(HGNC:PPP1R8)) View Subject | View Object

Appears in Networks:

Evidence 8d0ecf51b4
JSON

In addition, tau seems to be essential for axonal elongation and maturation, as knockdown of tau in cultured rat neurons inhibits neurite formation, whereas overexpression of tau promotes the formation of neurites even in non-neuronal cells1

p(HGNC:MAPT) increases a(MESH:Neurites) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

Evidence ab3e13f173
JSON

These studies indicate that the endogenous tau plays a part in regulating neuronal activity

p(HGNC:MAPT) regulates act(a(MESH:Neurons)) View Subject | View Object

Appears in Networks:

Evidence 8ad90d4782
JSON

Intraneuronal iron accumulation, neuronal loss in the substantia nigra and a severe decline in locomotor functions were observed in 12‑month-old tau-knockoutmice

p(HGNC:MAPT) increases a(MESH:Neurons) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Substantia Nigra

p(HGNC:MAPT) decreases a(CHEBI:"iron(0)") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT) increases bp(GO:locomotion) View Subject | View Object

Appears in Networks:

Evidence e6881b23f9
JSON

Although tau function can be partly compensated by other, redundant microtubule-associated proteins (for example, MAP1A), the behavioural impairments observed in aged (~12‑month-old) tau-knockout mice indicate that tau is necessary for normal neuronal and brain function.

p(HGNC:MAPT) increases act(a(MESH:Neurons)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT) increases act(a(MESH:Brain)) View Subject | View Object

Appears in Networks:

Evidence 941a6b9b3b
JSON

This study revealed that tau deficiency can cause iron accumulation inside neurons by preventing the trafficking of APP to the cell surface, where APP usually interacts with ferroportin (FPN) to facilitate the export of iron

p(HGNC:MAPT) decreases a(CHEBI:"iron(0)") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:MAPT) increases tloc(p(HGNC:APP), fromLoc(GO:cytoplasm), toLoc(GO:"cell surface")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

complex(p(HGNC:APP), p(HGNC:SLC40A1)) increases sec(a(CHEBI:"iron(0)")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

surf(p(HGNC:APP)) increases complex(p(HGNC:APP), p(HGNC:SLC40A1)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Neurons

Evidence cfcad71abc
JSON

A selective deficit in LTD but not in long-term potentiation (LTP) was observed in the CA1 region of the hippocampus in tau-knockout mice in vivo and ex vivo

p(HGNC:MAPT) increases bp(GO:"long-term synaptic depression") View Subject | View Object

Appears in Networks:
Annotations
MeSH
CA1 Region, Hippocampal

Evidence b6d083ce02
JSON

In addition, tau may interact with actin to induce aligned bundles of actin filaments, thus modifying the organization of the cytoskeleton network

p(HGNC:MAPT) directlyIncreases complex(a(MESH:Actins), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

complex(a(MESH:Actins), p(HGNC:MAPT)) increases a(GO:"actin filament bundle") View Subject | View Object

Appears in Networks:

complex(a(MESH:Actins), p(HGNC:MAPT)) regulates a(GO:"actin cytoskeleton") View Subject | View Object

Appears in Networks:

Evidence b8a33d9719
JSON

The reduction of tau levels in the brain causes dementia lacking distinctive histopathology (DLDH), the most common pathological variant of sporadic FTD

p(HGNC:MAPT) negativeCorrelation path(MESH:Dementia) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:Dementia) negativeCorrelation p(HGNC:MAPT) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence ce1ae99b76
JSON

In AD and other tauopathies, the increase in dendritic tau levels is one of the first and most overt pathological abnormalities

p(HGNC:MAPT) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dendritic Spines

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dendritic Spines

Evidence 284c03faba
JSON

In addition, dendritic tau could serve as a protein scaffold to deliver the kinase FYN to postsynaptic sites, where FYN phosphorylates subunit 2 of the NMDA receptor (NR2B; also known as GluN2B), resulting in the stabilization of the interaction of this receptor interaction with postsynaptic density protein 95 (PSD95; also known as DLG4), potentiating glutamatergic signalling and thereby enhancing Aβ toxicity.

p(HGNC:MAPT) increases act(a(CHEBI:"amyloid-beta")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dendritic Spines

p(HGNC:MAPT) increases complex(p(HGNC:DLG4), p(HGNC:FYN)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dendritic Spines

complex(p(HGNC:DLG4), p(HGNC:FYN)) increases act(a(GO:"glutamatergic synapse")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dendritic Spines

complex(p(HGNC:DLG4), p(HGNC:FYN)) increases act(a(CHEBI:"amyloid-beta")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dendritic Spines

p(HGNC:FYN) increases p(HGNC:GRIN2B, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dendritic Spines

p(HGNC:GRIN2B, pmod(Ph)) increases complex(p(HGNC:DLG4), p(HGNC:FYN)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Dendritic Spines

Evidence a88eda92d2
JSON

In the human brain, tau can be cleaved behind Thr123, generating an N‑terminally truncated, tau124–441 fragment. This fragment exhibits stronger affinity for microtubules than does full-length tau, presumably because the removal of the negatively charged N‑terminal domain enhances its binding to the negative surface of microtubules

p(HGNC:MAPT, frag("124_441")) directlyIncreases complex(a(GO:microtubule), p(HGNC:MAPT, frag("124_441"))) View Subject | View Object

Appears in Networks:

Evidence 437ec0bc97
JSON

Nevertheless, the interaction of tau with RNA may induce tau aggregation and thus contribute to neurodegeneration

complex(a(MESH:RNA), p(HGNC:MAPT)) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

complex(a(MESH:RNA), p(HGNC:MAPT)) increases path(HBP:Neurodegeneration) View Subject | View Object

Appears in Networks:

Evidence 07048241e5
JSON

It is worth noting that another non-coding miRNA, miR‑219, can bind directly to the 3ʹ untranslated region of tau mRNA and thereby repress tau synthesis at the post-transcriptional level, although it does not affect splicing of tau.

complex(g(HGNC:MIR219A1), p(HGNC:MAPT)) decreases p(HGNC:MAPT) View Subject | View Object

Appears in Networks:

g(HGNC:MIR219A1) increases complex(g(HGNC:MIR219A1), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

Evidence 4e7a52d496
JSON

In addition, tau can be phosphorylated by tyrosine kinases such as the SRC family members LCK, SYK and FYN at Tyr18, and the ABL family members ARG and ABL1 at Tyr394 (REF. 45).

p(HGNC:FYN) directlyIncreases p(HGNC:MAPT, pmod(Ph, Tyr, 18)) View Subject | View Object

Appears in Networks:

p(HGNC:ABL1) directlyIncreases p(HGNC:MAPT, pmod(Ph, Tyr, 394)) View Subject | View Object

Appears in Networks:

p(HGNC:ABL2) directlyIncreases p(HGNC:MAPT, pmod(Ph, Tyr, 394)) View Subject | View Object

Appears in Networks:

p(HGNC:LCK) directlyIncreases p(HGNC:MAPT, pmod(Ph, Tyr, 18)) View Subject | View Object

Appears in Networks:

p(HGNC:SYK) directlyIncreases p(HGNC:MAPT, pmod(Ph, Tyr, 18)) View Subject | View Object

Appears in Networks:

Evidence 2e62c4189b
JSON

For instance, hyperphosphorylated tau can interact with JIP1 and thus impair the formation of kinesin complex

complex(p(HGNC:MAPK8IP1), p(HGNC:MAPT, pmod(HBP:hyperphosphorylation))) decreases complex(GO:"kinesin complex") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) increases complex(p(HGNC:MAPK8IP1), p(HGNC:MAPT, pmod(HBP:hyperphosphorylation))) View Subject | View Object

Appears in Networks:

Evidence a03afb06e6
JSON

Notably, as aggregated tau in patients with a tauopathy or in transgenic mice invariably show hyperphosphorylation, and tau hyperphosphorylation precedes aggregation, phosphorylation has been assumed to drive tau aggregation

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence efd966e889
JSON

Hyperphosphorylation of tau at the repeat domain reduces its microtubule binding, which may cause microtubule disassembly, leading to axonal transport deficits.

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

Appears in Networks:

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

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) decreases bp(GO:"axonal transport") View Subject | View Object

Appears in Networks:

Evidence aff41e4b10
JSON

In a Drosophila melanogaster model of tauopathy, the hyperphosphorylation of tau led to the abnormal alignment and accumulation of F‑actin filaments, and thereby induced neurodegeneration

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) increases complex(GO:"filamentous actin") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) increases path(HBP:Neurodegeneration) View Subject | View Object

Appears in Networks:

Evidence 60d3e17720
JSON

For instance, miR‑132, which is downregulated in PSP, reduces 4R tau expression in mouse neuroblastoma cells.

g(HGNC:MIR132) negativeCorrelation path(MESH:"Supranuclear Palsy, Progressive") View Subject | View Object

Appears in Networks:

g(HGNC:MIR132) decreases p(HBP:"4R tau") View Subject | View Object

Appears in Networks:

path(MESH:"Supranuclear Palsy, Progressive") negativeCorrelation g(HGNC:MIR132) View Subject | View Object

Appears in Networks:

Evidence 44ff4dea64
JSON

Other phosphorylation sites in or near the repeat domain are phosphorylated by microtubule affinity-regulating kinases (MARKs; also known as PAR1 kinases), cyclic AMP-dependent protein kinase (PKA) and Ca2+- or calmodulin-dependent protein kinase II (CaMKII), among others

p(FPLX:PKA) directlyIncreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:CAMK2A) directlyIncreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:MARK1) directlyIncreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

Evidence 4b84bb5801
JSON

For example,the phosphorylation of KXGS motifs (particularly Ser262) in the repeat domain of tau by MARK, PKA or CaMKII can reduce the affinity of tau to microtubules

p(HGNC:MARK1) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 262)) View Subject | View Object

Appears in Networks:

p(FPLX:PKA) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 262)) View Subject | View Object

Appears in Networks:

p(HGNC:CAMK2A) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 262)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 262)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

Evidence 29e75cd797
JSON

The two short hexapeptide motifs VQIINK and VQIVYK at the beginning of R2 and R3, respectively, show propensity for forming β‑sheet structures and are essential for tau aggregation, even though they comprise only a tiny fraction of the sequence

p(HBP:"VQIINK motif") increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HBP:"VQIVYK motif") increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence fd1326ada8
JSON

Disruption of these motifs (for example, by Pro mutations) abrogates the tendency for tau to aggregate; by contrast, strengthening the β‑structure with certain mutations (for instance, ΔK280 or P301L) accelerates tau aggregation both in vitro and in vivo

p(HBP:"VQIINK motif") increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HBP:"VQIVYK motif") increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Lys280del")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Pro301Leu")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence 9e5d9c3d3c
JSON

The motif VQIVYK has been shown to be sufficient to form fibrils composed of steric ‘zippers’ formed by two tightly interdigitated β‑sheets.

p(HBP:"VQIVYK motif") increases a(HBP:"Tau fibrils") View Subject | View Object

Appears in Networks:

Evidence 27fb01e071
JSON

For instance, the phosphorylation of tau at Ser422 inhibits the cleavage of tau by caspase 3 at Asp421

p(HGNC:CASP3) increases p(HGNC:MAPT, frag("?")) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Ser, 422)) decreases p(HGNC:MAPT, frag("?")) View Subject | View Object

Appears in Networks:

Evidence a726f4c080
JSON

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

p(HGNC:CASP3) increases p(HGNC:MAPT, frag("1_421")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:MAPT, frag("1_421")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

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

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

Evidence 6914457aae
JSON

Tau can be acetylated by the P300 acetyltransferase or by CREB-binding protein at several Lys residues in the flanking region or the repeat domain, and deacetylated at these sites by sirtuin 1 (SIRT1) and histone deacetylase 6 (HDAC6), respectively

p(HGNC:CREBBP) increases p(HGNC:MAPT, pmod(Ac, Lys)) View Subject | View Object

Appears in Networks:

p(HGNC:EP300) increases p(HGNC:MAPT, pmod(Ac, Lys)) View Subject | View Object

Appears in Networks:

p(HGNC:HDAC6) decreases p(HGNC:MAPT, pmod(Ac, Lys)) View Subject | View Object

Appears in Networks:

p(HGNC:SIRT1) decreases p(HGNC:MAPT, pmod(Ac, Lys)) View Subject | View Object

Appears in Networks:

Evidence 05278646fb
JSON

In a cellular model of tauopathy, cells expressing the ΔK280 repeat-domain-mutant tau show tau aggregation that depends on the stepwise proteolysis of the N‑terminal domain by a thrombin-like protease and of the C‑terminal domain by cathepsin L, generating a fragment (F3) that leads to robust aggregation in cell and animal models

p(HGNC:CTSL) increases p(HGNC:MAPT, frag("258_360")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Tauopathies

p(HGNC:F2) increases p(HGNC:MAPT, frag("258_360")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Tauopathies

p(HGNC:MAPT, frag("258_360")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Tauopathies

p(HGNC:MAPT, var("p.Lys280del")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Tauopathies

Evidence d6266fd050
JSON

Notably, two proteins — 14‑3‑3ζ and immunophilin (also known as FKBP52 or FKBP4) — have also been shown to induce aggregation of recombinant tau in vitro, presumably by stabilizing an aggregation-prone conformation of tau.

p(HGNC:FKBP4) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HGNC:YWHAZ) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence 00c96876ce
JSON

Indeed, knockdown of FUS increases the expression of the 2N and 4R tau isoforms, providing a possible link between frontotemporal lobar degeneration-FUS (FTLDFUS; a subtype of FTD characterized by FUS inclusions in neurons and glia) and FTLD-tau (a tauopathy).

p(HGNC:FUS) decreases p(HBP:"4R tau") View Subject | View Object

Appears in Networks:

p(HGNC:FUS) decreases p(HBP:"Tau isoform F (441 aa)") View Subject | View Object

Appears in Networks:

p(HGNC:FUS) decreases p(HBP:"Tau isoform C (410 aa)") View Subject | View Object

Appears in Networks:

p(HGNC:FUS) association path(MESH:"Frontotemporal Lobar Degeneration") View Subject | View Object

Appears in Networks:

path(MESH:"Frontotemporal Lobar Degeneration") association p(HGNC:FUS) View Subject | View Object

Appears in Networks:

Evidence b90207c2cc
JSON

One of these fragments was identified as tau151–391, which is prone to aggregation, as rats transgenic for this fragment develop neurofibrillary pathology; the identity of the other fragment remains unclear

p(HGNC:MAPT, frag("151_391")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence 054d19ffd4
JSON

The truncation of tau at Asn368 has been observed in human AD brains and in a P301S mouse model of tauopathy, in which it leads to the generation of a tau1–368 fragment that is prone to aggregation and shows compromised microtubule-assembly activity, possibly contributing to tau aggregation and neurodegeneration.

p(HGNC:MAPT, frag("1_368")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:MAPT, frag("1_368")) increases path(HBP:Neurodegeneration) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:MAPT, frag("1_368")) decreases bp(GO:"microtubule polymerization") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

Evidence 2cba670aeb
JSON

For instance, a 20–22-kDa N‑terminal tau fragment (amino acids 26–230) was detected in an AD mouse model expressing a transgenic nerve growth factor (NGF)-specific antibody (AD11) and in the cerebrospinal fluid (CSF) of individuals with AD is neurotoxic in primary neurons

p(HGNC:MAPT, frag("26_230")) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, frag("26_230")) View Subject | View Object

Appears in Networks:

Evidence e2cfce4eb8
JSON

Truncation of tau prevents the formation of this structure and might thereby promote tau aggregation

p(HGNC:MAPT, frag("?")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence e031dd630b
JSON

Truncation of tau could generate tau fragments with a higher tendency for aggregation (see below), probably owing to the disruption of the paperclip structure of tau, as described above.

p(HGNC:MAPT, frag("?")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence 4a368728b9
JSON

Truncated tau fragments that contain the repeat domain have a higher tendency for aggregation, probably owing to the disruption of the usual paperclip structure

p(HGNC:MAPT, frag("?")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence 3371f5a09f
JSON

In addition, the truncation of tau may result in tau fragments that induce neurodegeneration independently of tau aggregation.

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

Appears in Networks:

Evidence c39cd5cf3d
JSON

Depending on the sites, the acetylation of tau could inhibit its degradation (for example, when at Lys163, Lys280, Lys281 or Lys369) or, by contrast, facilitate its degradation and suppress its phosphorylation and aggregation (for example, when at Lys259, Lys290, Lys321 or Lys353)

p(HGNC:MAPT, pmod(Ac, Lys, 163)) decreases deg(p(HGNC:MAPT, pmod(Ac, Lys, 163))) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 259)) increases deg(p(HGNC:MAPT, pmod(Ac, Lys, 259))) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 259)) decreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 259)) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 280)) decreases deg(p(HGNC:MAPT, pmod(Ac, Lys, 280))) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 281)) decreases deg(p(HGNC:MAPT, pmod(Ac, Lys, 281))) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 290)) increases deg(p(HGNC:MAPT, pmod(Ac, Lys, 290))) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 290)) decreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 290)) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 321)) increases deg(p(HGNC:MAPT, pmod(Ac, Lys, 321))) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 321)) decreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 321)) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 353)) increases deg(p(HGNC:MAPT, pmod(Ac, Lys, 353))) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 353)) decreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 353)) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 369)) decreases deg(p(HGNC:MAPT, pmod(Ac, Lys, 369))) View Subject | View Object

Appears in Networks:

Evidence dc7c4926c5
JSON

Recently, tau acetylation at Lys174 was identified in human AD brains as well.

p(HGNC:MAPT, pmod(Ac, Lys, 174)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ac, Lys, 174)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence ca9032afb4
JSON

By contrast, acetylation of tau at Lys280 has been detected in AD and other tauopathies, including AGD, tangle-predominant senile dementia (TPSD), PiD, FTDP‑17 and PSP, and is pathological

p(HGNC:MAPT, pmod(Ac, Lys, 280)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 280)) positiveCorrelation path(MESH:"Niemann-Pick Diseases") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 280)) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 280)) positiveCorrelation path(MESH:"Supranuclear Palsy, Progressive") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ac, Lys, 280)) View Subject | View Object

Appears in Networks:

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:MAPT, pmod(Ac, Lys, 280)) View Subject | View Object

Appears in Networks:

path(MESH:"Niemann-Pick Diseases") positiveCorrelation p(HGNC:MAPT, pmod(Ac, Lys, 280)) View Subject | View Object

Appears in Networks:

path(MESH:"Supranuclear Palsy, Progressive") positiveCorrelation p(HGNC:MAPT, pmod(Ac, Lys, 280)) View Subject | View Object

Appears in Networks:

Evidence 4c6e0800af
JSON

Non-enzymatic post-translational modifications, including glycation, deamidation and isomerization, are detected in PHF-tau but not in normal tau. All of these modifications may facilitate tau aggregation

p(HGNC:MAPT, pmod(GO:"protein peptidyl-prolyl isomerization")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:"non-enzymatic protein modifications")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:glycation)) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence 9746fbc788
JSON

In addition, glycation of tau may reduce the binding of tau to microtubules

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

Appears in Networks:

Evidence 8a4b1bd175
JSON

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

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

Evidence 73fe9058a7
JSON

The nitration of these Tyr residues alters the conformation of tau, reduces its binding to microtubules and, depending on the nitration sites, can promote or inhibit aggregation

p(HGNC:MAPT, pmod(HBP:nitration, Tyr, 18)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:nitration, Tyr, 29)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:nitration, Tyr, 394)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

Evidence 62d5e3aff1
JSON

In human AD brains, PHF-tau is methylated at fewer sites than is tau from normal human brains

p(HGNC:MAPT, pmod(Me)) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") negativeCorrelation p(HGNC:MAPT, pmod(Me)) View Subject | View Object

Appears in Networks:

Evidence 2fc4759d7a
JSON

Lysine methylation is another endogenous post-translational modification of tau in the human brain, and in vitro studies have shown that methylation of tau suppresses its aggregation

p(HGNC:MAPT, pmod(Me, Lys)) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence 2ad070e1fd
JSON

In human AD brains, but not in normal brains, tau is modified by N‑glycosylation, which is proposed to help to maintain and stabilize PHF structure

p(HGNC:MAPT, pmod(NGlyco)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

p(HGNC:MAPT, pmod(NGlyco)) regulates a(HBP:"paired helical filaments") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(NGlyco)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence 224d9e0ab0
JSON

Furthermore, N‑glycosylation may facilitate tau hyperphosphorylation, as it suppresses the dephosphorylation and accelerates the phosphorylation of tau, probably because it changes the conformation of tau

p(HGNC:MAPT, pmod(NGlyco)) increases p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(NGlyco)) increases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

Evidence b7e94dbead
JSON

In contrast to N‑glycosylation, O‑GlcNAcylation (a type of O‑glycosylation) of tau may protect it against phosphorylation, as it occupies the Ser or Thr residue of Ser‑Pro or Thr-Pro motifs

p(HGNC:MAPT, pmod(OGlyco)) decreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

Evidence 1e060a373d
JSON

In addition, O‑GlcNAcylation of tau can suppress tau aggregation

p(HGNC:MAPT, pmod(OGlyco)) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence 7e046f883d
JSON

In AD, the O‑GlcNAcylation of tau is reduced — an effect that might contribute to the hyperphosphorylation and aggregation of tau

path(MESH:"Alzheimer Disease") decreases p(HGNC:MAPT, pmod(OGlyco)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(OGlyco)) decreases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(OGlyco)) decreases p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

Appears in Networks:

Evidence 9f059f35ab
JSON

In AD, the phosphorylation of tau is increased further to approximately eight phosphates per molecule.

p(HGNC:MAPT, pmod(Ph)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

Evidence bb7ed49c25
JSON

This view is supported by a recent study showing that tau in a normal mouse brain is phosphorylated at many sites that were previously found to be phosphorylated in tau from the brains of patients with AD.

p(HGNC:MAPT, pmod(Ph)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence b8edbafe2a
JSON

The phosphorylation of tau appears to alter its association with actin, as tau phosphorylated at the KXGS motifs tends to colocalize with actin filaments in growth cones during development and in rod-like inclusions of cofilin and actin

p(HGNC:MAPT, pmod(Ph)) decreases complex(a(MESH:Actins), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

Evidence bbae16f517
JSON

In addition, phosphorylation of Ser214 and Thr231 in the flanking region of tau can trigger the detachment of tau from microtubules, whereas phosphorylation at other Thr-Pro or Ser-Pro motifs in the flanking region has only a weak influence on tau–microtubule binding

p(HGNC:MAPT, pmod(Ph, Ser, 214), pmod(Ph, Thr, 231)) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

Evidence 1e69b896c1
JSON

In a line of the JNPL3 tauopathy mouse model, which expresses human 0N4R tau bearing the missense P301L mutation, the overall increase in Tyr phosphorylation of tau correlated with the formation of tau aggregates, suggesting that overall Tyr phosphorylation might contribute to tau aggregation

p(HGNC:MAPT, pmod(Ph, Tyr)) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence 1c1be63790
JSON

In familial tauopathies, the mutation of MAPT seems to be the cause of tau aggregation, but in sporadic tauopathies (such as AD), the trigger of tau pathology is unclear.

p(HGNC:MAPT, var("?")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence c85bd960f2
JSON

Interestingly, the PSP-associated tau mutation A152T is localized far away from the repeat domain but still decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently

p(HGNC:MAPT, var("p.Ala152Thr")) positiveCorrelation path(MESH:"Supranuclear Palsy, Progressive") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Ala152Thr")) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Ala152Thr")) decreases bp(GO:"microtubule polymerization") View Subject | View Object

Appears in Networks:

path(MESH:"Supranuclear Palsy, Progressive") positiveCorrelation p(HGNC:MAPT, var("p.Ala152Thr")) View Subject | View Object

Appears in Networks:

Evidence 808079e22f
JSON

In addition, this A152T tau enhances the formation of oligomers but not fibres

p(HGNC:MAPT, var("p.Ala152Thr")) increases a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:

Evidence f113be8dbd
JSON

Some tau mutations (such as A152T and R5H) may cause loss of tau function as well (as discussed above)

p(HGNC:MAPT, var("p.Ala152Thr")) decreases act(p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Arg5His")) decreases act(p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

Evidence 8dfa70696d
JSON

Tau protein with mutations in or near the microtubule-binding domain (for instance, G272V, N279K, ΔK280, P301L, V337M or R406W) tend to have a reduced affinity for microtubules and an increased tendency for aggregation

p(HGNC:MAPT, var("p.Arg406Trp")) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Arg406Trp")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Asn279Lys")) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Asn279Lys")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Gly272Val")) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Gly272Val")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Lys280del")) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Lys280del")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Pro301Leu")) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Pro301Leu")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Val337Met")) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Val337Met")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:

Evidence a2646e0b4e
JSON

Another mutation (R5H or R5L) outside the microtubule-binding domain disrupts the binding of tau to the p150 subunit of the dynactin complex — an essential cofactor for the microtubule motor dynein —thereby possibly interfering with general axonal transport

p(HGNC:MAPT, var("p.Arg5His")) decreases complex(p(HGNC:DCTN1), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Arg5His")) decreases bp(GO:"axonal transport") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Arg5Leu")) decreases complex(p(HGNC:DCTN1), p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Arg5Leu")) decreases bp(GO:"axonal transport") View Subject | View Object

Appears in Networks:

Evidence 451296b278
JSON

However, there are also other mutations (such as ΔK280, L266V and G272V) that inhibit the inclusion of E10 and thus reduce the 4R-to-3R ratio

p(HGNC:MAPT, var("p.Leu266Val")) decreases p(HBP:"4R tau") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Leu266Val")) increases p(HBP:"3R tau") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Gly272Val")) decreases p(HBP:"4R tau") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Gly272Val")) increases p(HBP:"3R tau") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Lys280del")) decreases p(HBP:"4R tau") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Lys280del")) increases p(HBP:"3R tau") View Subject | View Object

Appears in Networks:

Evidence 9972b6a87c
JSON

Remarkably, in two regulatable transgenic mouse models expressing human tau with the P301L mutation (rTg4510) or expressing the repeat domain of tau with the ΔK280 mutation, switching off tau expression improved memory impairment even though NFTs remained, clearly showing that tau aggregates are not sufficient for neurodegeneration and the cognitive effects that are typically observed in these models

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

Appears in Networks:

p(HGNC:MAPT, var("p.Pro301Leu")) increases bp(GO:memory) View Subject | View Object

Appears in Networks:

Evidence bb252531be
JSON

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

p(HGNC:MAPT, var("p.Lys280del")) increases tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(GO:"somatodendritic compartment")) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, var("p.Lys280del")) increases p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

Evidence 6b751bec36
JSON

Protein phosphatase 1 (PP1), PP2A, PP2B, PP2C and PP5 have all been implicated in the dephosphorylation of tau

p(HGNC:PPP2CA) directlyDecreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:PPM1A) directlyDecreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:PPP1R8) directlyDecreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:PPP3CB) directlyDecreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:PPP5C) directlyDecreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

Evidence 6d59fd403f
JSON

Among them, PP2A is the main phosphatase:it accounts for ~70% of the human brain tau phosphatase activity, and its activity is reduced in the AD brain (by ~20% and ~40% in the grey and white matter, respectively)

p(HGNC:PPP2CA) directlyDecreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

act(p(HGNC:PPP2CA)) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") negativeCorrelation act(p(HGNC:PPP2CA)) View Subject | View Object

Appears in Networks:

Evidence dfc6fdad0c
JSON

Intriguingly, SRSF2 levels are increased in the brains of individuals with PSP.

p(HGNC:SRSF2) positiveCorrelation path(MESH:"Supranuclear Palsy, Progressive") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:"Supranuclear Palsy, Progressive") positiveCorrelation p(HGNC:SRSF2) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Brain

Evidence 784b18c85f
JSON

Acetylation at Lys259, Lys290, Lys321 or Lys353 within the KXGS motifs occurs in normal tau, and is reduced in brains of individuals with AD and of rTg4510 transgenic mice

path(MESH:"Alzheimer Disease") decreases p(HGNC:MAPT, pmod(Ac, Lys, 259)) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") decreases p(HGNC:MAPT, pmod(Ac, Lys, 290)) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") decreases p(HGNC:MAPT, pmod(Ac, Lys, 321)) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") decreases p(HGNC:MAPT, pmod(Ac, Lys, 353)) View Subject | View Object

Appears in Networks:

Evidence 8334f2407e
JSON

The truncation of tau occurs in AD and in other tauopathies

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

Appears in Networks:

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

Appears in Networks:

Evidence 77b0044e99
JSON

Notably, this accumulation of iron was observed in the brain regions with reduced soluble tau levels, such as the cortex in AD, the substantia nigra in PD and various brain regions in several other tauopathies

path(MESH:"Alzheimer Disease") increases a(CHEBI:"iron(0)") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Cerebral Cortex

path(MESH:"Parkinson Disease") increases a(CHEBI:"iron(0)") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Substantia Nigra

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.