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PubMed: 29191965

Title
<i>Caenorhabditis elegans</i> models of tauopathy.
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
31
Issue
None
Pages
5137-5148
Date
2017-12-01
Authors
Choudhary B | Mandelkow E | Pir GJ

Evidence c1803ce402
JSON

In a recent study, tau was reported to impair neurotransmission at the presynapse by binding and inhibiting synaptic vesicle transport and release, an effect mediated by the N-terminal domain (78).

complex(a(GO:"synaptic vesicle"), p(HGNC:MAPT)) decreases act(a(GO:"synaptic vesicle")) View Subject | View Object

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complex(a(GO:"synaptic vesicle"), p(HGNC:MAPT)) decreases bp(MESH:"Synaptic Transmission") View Subject | View Object

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Evidence 4ef59d9a5c
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For example, Fatouros et al. (68) tested several tau-aggregation inhibitor compounds such as methylene blue, a rhodanine derivative (bb14), and a phenylthiazolyl hydrazide derivative (BSc3094), which reduce the insoluble tau and partially suppress the Unc phenotype.

a(CHEBI:"methylene blue") decreases a(HBP:"Tau aggregates") View Subject | View Object

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a(CHEBI:"methylene blue") positiveCorrelation bp(GO:locomotion) View Subject | View Object

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a(HBP:"Phenylthiazolyl-hydrazide") decreases a(HBP:"Tau aggregates") View Subject | View Object

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a(HBP:"Phenylthiazolyl-hydrazide") positiveCorrelation bp(GO:locomotion) View Subject | View Object

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a(PUBCHEM:6475963) decreases a(HBP:"Tau aggregates") View Subject | View Object

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a(PUBCHEM:6475963) positiveCorrelation bp(GO:locomotion) View Subject | View Object

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bp(GO:locomotion) positiveCorrelation a(CHEBI:"methylene blue") View Subject | View Object

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bp(GO:locomotion) positiveCorrelation a(PUBCHEM:6475963) View Subject | View Object

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bp(GO:locomotion) positiveCorrelation a(HBP:"Phenylthiazolyl-hydrazide") View Subject | View Object

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Evidence 0fe5514086
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The antipsychotic drug azaperone shows neuroprotective effects, improves locomotion, reduces the insoluble tau, and partially abates the neurodegeneration in this tauopathy model (104).

a(CHEBI:azaperone) increases bp(GO:locomotion) View Subject | View Object

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a(CHEBI:azaperone) decreases p(HGNC:MAPT) View Subject | View Object

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a(CHEBI:azaperone) decreases path(HBP:Neurodegeneration) View Subject | View Object

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Evidence ebb3e6e366
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Tau lines described by Miyasaka et al. show tau accumulations predominantly in the cell bodies as seen by immunostaining (62).

a(GO:"cell body") association p(HGNC:MAPT) View Subject | View Object

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p(HGNC:MAPT) association a(GO:"cell body") View Subject | View Object

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Evidence 8223d0563d
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Tien et al. (50) showed a physical interaction of PTL-1 with Kinesin-3/UNC-104, a major motor for synaptic vesicle proteins and dense core vesicles in C. elegans.

a(GO:"synaptic vesicle") association complex(p(HGNC:KLC3), p(HGNC:MAPT)) View Subject | View Object

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p(HGNC:MAPT) directlyIncreases complex(p(HGNC:KLC3), p(HGNC:MAPT)) View Subject | View Object

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complex(p(HGNC:KLC3), p(HGNC:MAPT)) association a(GO:"synaptic vesicle") View Subject | View Object

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Evidence 28bba4dec4
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One exception is the report of the accumulation of tau aggregates in presynaptic boutons in transgenic mice, whereby it induces synaptic dysfunction and loss of presynapses (77).

a(HBP:"Tau aggregates") decreases act(a(GO:synapse)) View Subject | View Object

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Annotations
MeSH
Presynaptic Terminals

a(HBP:"Tau aggregates") decreases a(GO:presynapse) View Subject | View Object

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Annotations
MeSH
Presynaptic Terminals

Evidence 613a5e0ef7
JSON

Nonetheless, it is assumed that tau aggregation may be driven by phosphorylation at certain sites (95), whereas phosphorylation at other sites may inhibit aggregation (96).

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

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

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Evidence 7164bcc393
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Indeed, evidence from both human and mouse studies indicates that soluble oligomers rather than insoluble aggregates are toxic to normal neurons (70).

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

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Evidence 7a7c546678
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Another compound of the ATPZ class also is protective and partially ameliorates the neurodegeneration in this tauopathy model.

a(PUBCHEM:66766582) decreases path(HBP:Neurodegeneration) View Subject | View Object

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Evidence cf09c7044d
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Indeed, aggresome formation represents one such process employed by a cell to discard misfolded proteins (125) and has been implicated in neurodegenerative diseases (126).

bp(GO:"aggresome assembly") association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

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bp(GO:"aggresome assembly") decreases p(MESH:Proteins, pmod(HBP:misfolding)) View Subject | View Object

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path(MESH:"Neurodegenerative Diseases") association bp(GO:"aggresome assembly") View Subject | View Object

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Evidence 094c245d15
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Thus, TauA152T affects both neuronal aging and whole organism lifespan

bp(GO:"cell aging") negativeCorrelation p(HBP:"Tau isoform F (441 aa)", var("p.Ala152Thr")) View Subject | View Object

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Annotations
MeSH
Neurons

p(HBP:"Tau isoform F (441 aa)", var("p.Ala152Thr")) negativeCorrelation bp(GO:"cell aging") View Subject | View Object

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Annotations
MeSH
Neurons

p(HBP:"Tau isoform F (441 aa)", var("p.Ala152Thr")) decreases bp(MESH:Longevity) View Subject | View Object

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Annotations
MeSH
Neurons

Evidence 45c5a063ee
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A recent study, Krieg et al. (49), established the role of PTL-1 in the maintenance and repair of the microtubule cytoskeleton after transient damage induced by mechanical stress. This process requires other microtubule-associated proteins such as b-spectrin.

bp(GO:"cellular response to mechanical stimulus") decreases a(GO:"microtubule cytoskeleton") View Subject | View Object

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composite(p(HGNC:MAPT), p(HGNC:SPTB)) regulates a(GO:"microtubule cytoskeleton") View Subject | View Object

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Evidence 64741ee2f7
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In a recent study, the antiepileptic drug ethosuximide increased the lifespan and partially corrected the Unc phenotype in TauV337M worms with the effect dependent on the insulin signaling pathway (106).

bp(GO:"insulin receptor signaling pathway") positiveCorrelation composite(a(CHEBI:ethosuximide), p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met"))) View Subject | View Object

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composite(a(CHEBI:ethosuximide), p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met"))) increases bp(MESH:Longevity) View Subject | View Object

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composite(a(CHEBI:ethosuximide), p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met"))) increases bp(GO:locomotion) View Subject | View Object

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composite(a(CHEBI:ethosuximide), p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met"))) positiveCorrelation bp(GO:"insulin receptor signaling pathway") View Subject | View Object

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Evidence e2a963f850
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Three transgenic lines were generated based on 1N4R wild-type MAPT or its FTD-17 mutant variants P301L and V337M. The mutant lines showed a stronger Unc phenotype than the wild-type tau lines and the severity of the Unc phenotype progressed with age

bp(GO:aging) decreases bp(GO:locomotion) View Subject | View Object

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p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")) decreases bp(GO:locomotion) View Subject | View Object

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p(HBP:"Tau isoform E (412 aa)", var("p.Pro301Leu")) decreases bp(GO:locomotion) View Subject | View Object

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Evidence 4647e7a719
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Genetic interaction studies involving ptl-1 and mutants in other genes associated with microtubules such as mec-12 (a-tubulin) and mec-7 (btubulin), suggested a larger functional role of PTL-1 in mechanosensation (45).

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

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p(HGNC:MAPT) increases complex(p(HGNC:MAPT), p(HGNC:TUBA1A)) View Subject | View Object

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

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Evidence fb509b44c9
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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

p(HGNC:DNMBP) increases complex(p(HGNC:DNMBP), p(HGNC:ENAH)) View Subject | View Object

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

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Evidence b50f066a40
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This worm also shows reduced survival, accumulates detergent-insoluble tau, and undergoes late-onset neurodegeneration (66)

p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")) decreases a(MESH:Survival) View Subject | View Object

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p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")) increases path(HBP:Neurodegeneration) View Subject | View Object

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p(HBP:"Tau isoform E (412 aa)", var("p.Pro301Leu")) decreases a(MESH:Survival) View Subject | View Object

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p(HBP:"Tau isoform E (412 aa)", var("p.Pro301Leu")) increases path(HBP:Neurodegeneration) View Subject | View Object

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Evidence f980d26d0f
JSON

For example, the first transgenic C. elegans human disease model was based on the expression of the AD-associated Ab peptide in body wall muscles, resulting in paralysis that could be suppressed by coexpression of transthyretin (29).

composite(a(MESH:"Amyloid beta-Peptides"), a(PUBCHEM:160718443)) decreases path(MESH:Paralysis) View Subject | View Object

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Evidence 0968c0bbb2
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As a result, the proaggregant lines showed a range of defects including paralysis, axonal degeneration of GABAergic and cholinergic motor neurons, presynaptic defects, synapse loss, and mitochondrial transport defects early in adulthood

composite(p(HBP:"4R tau", var("p.Lys280del")), p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met"))) increases path(MESH:Paralysis) View Subject | View Object

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composite(p(HBP:"4R tau", var("p.Lys280del")), p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met"))) decreases a(MESH:"GABAergic Neurons") View Subject | View Object

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composite(p(HBP:"4R tau", var("p.Lys280del")), p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met"))) decreases a(MESH:"Cholinergic Neurons") View Subject | View Object

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composite(p(HBP:"4R tau", var("p.Lys280del")), p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met"))) decreases a(GO:synapse) View Subject | View Object

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composite(p(HBP:"4R tau", var("p.Lys280del")), p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met"))) decreases bp(GO:"axonal transport of mitochondrion") View Subject | View Object

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Evidence e2564110e3
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Similarly, elimination of CDK-5 improved the touch response in the mutant TauR406W-line, but failed to improve it inother line

composite(p(HBP:"Tau isoform D (383 aa)", var("p.Pro301Leu")), p(HGNC:CDK5)) decreases a(MESH:Neurons) View Subject | View Object

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Evidence a3555b4ae4
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Frontotemporal dementia with parkinsonism–mutant tau expression (0N4R-tau P301L and 0N4R-tau R406W), on the other hand, resulted in a reduced touch response that worsened with age

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

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MeSH
Frontotemporal Dementia

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

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Annotations
MeSH
Frontotemporal Dementia

Evidence 95861dccca
JSON

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).

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

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

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p(HBP:"Tau isoform D (383 aa)", var("p.Pro301Leu")) increases bp(GO:"neuron death") View Subject | View Object

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

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

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p(HBP:"Tau isoform D (383 aa)", var("p.Arg406Trp")) increases bp(GO:"neuron death") View Subject | View Object

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Evidence d74fa60b30
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The responsible kinases include 1) proline-directed protein kinases (PDPKs) targeting SP or TP motifs [e.g., GSK3b, cyclindependent kinase (CDK)-5, and MAPKs]; 2) non–proline directed protein kinases targeting KXGS-motifs [e.g., PKA, microtubule affinity-regulating kinase and synapses of the amphid defective (SADK)]; 3) protein kinases specific for tyrosines (e.g., Src, Lck, Syk, Fyn, and c-Abl kinase) (91).

p(HGNC:CDK5) directlyIncreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

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

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

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

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

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p(HGNC:GSK3B) directlyIncreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

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

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

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

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Evidence 7aee0eb2ba
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Indeed, 2 of the candidates identified in an RNAi screen that worsened the Unc phenotype in the TauV337M worm, called enhancers of tauopathy, were postsynaptic (80).

composite(p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")), p(HGNC:BAIAP3)) decreases bp(GO:locomotion) View Subject | View Object

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composite(p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")), p(HGNC:CHRNA7)) decreases bp(GO:locomotion) View Subject | View Object

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Evidence 7d82ad2094
JSON

AEX-1, predominantly expressed in muscles and intestine, regulates the retrograde signaling at neuromuscular junctions and is required for the normal localization of synaptic vesicle fusion protein UNC-13

p(HGNC:BAIAP3) regulates bp(GO:"retrograde trans-synaptic signaling") View Subject | View Object

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Annotations
MeSH
Neuromuscular Junction

Evidence fd4a40f18b
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acr-14 controls body movement by modulating the synaptic inputs and outputs of the ventral cord neural circuitry (83).

p(HGNC:CHRNA7) regulates act(a(GO:synapse)) View Subject | View Object

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p(HGNC:CHRNA7) regulates bp(GO:"musculoskeletal movement") View Subject | View Object

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Evidence c3b6eb7f71
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AD brains show an upregulation of CHRNA7 (acr-14 homolog in humans) (84), where it may mediate the Ab-induced tau pathology (85).

p(HGNC:CHRNA7) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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MeSH
Brain

p(HGNC:CHRNA7) regulates act(a(CHEBI:"amyloid-beta")) View Subject | View Object

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MeSH
Brain

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:CHRNA7) View Subject | View Object

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Annotations
MeSH
Brain

Evidence 26d4035509
JSON

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.

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

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

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

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

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

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

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

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

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

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

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

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

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Evidence 119b8d1617
JSON

Loss of bas-1 function improved the motor function, reduced insoluble tau and its phosphorylation and ameliorated the tau-induced neurodegeneration without increasing the longevity in TauV337M worms

composite(p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")), p(HGNC:DDC)) decreases bp(GO:locomotion) View Subject | View Object

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composite(p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")), p(HGNC:DDC)) increases p(HGNC:MAPT) View Subject | View Object

Appears in Networks:

composite(p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")), p(HGNC:DDC)) increases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Appears in Networks:

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

Appears in Networks:

Evidence 4e2d6a6515
JSON

A recent addition to the suppressors of tau-induced toxicity in C. elegans is the bas-1 gene (105), encoding the dopa decarboxylase, loss of which reduces the dopamine and serotonin levels (128–130).

p(HGNC:DDC) increases a(CHEBI:dopamine) View Subject | View Object

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p(HGNC:DDC) increases a(CHEBI:serotonin) View Subject | View Object

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Evidence 71cb6011fa
JSON

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)

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

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p(HGNC:GCH1) regulates a(CHEBI:dopamine) View Subject | View Object

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p(HGNC:GCH1) regulates a(CHEBI:serotonin) View Subject | View Object

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p(HGNC:GCH1) regulates act(p(HGNC:DDC)) View Subject | View Object

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

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p(HGNC:TH) regulates a(CHEBI:dopamine) View Subject | View Object

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p(HGNC:TH) regulates a(CHEBI:serotonin) View Subject | View Object

Appears in Networks:

p(HGNC:TH) regulates act(p(HGNC:DDC)) View Subject | View Object

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

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p(HGNC:TPH1) regulates a(CHEBI:dopamine) View Subject | View Object

Appears in Networks:

p(HGNC:TPH1) regulates a(CHEBI:serotonin) View Subject | View Object

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p(HGNC:TPH1) regulates act(p(HGNC:DDC)) View Subject | View Object

Appears in Networks:

Evidence 6ce331757d
JSON

Eliminating sut-2 resulted in partial recovery of Unc phenotype, less neurodegeneration and reduction of insoluble tau in the TauV337M worm; whereas sut-2 overexpression exacerbated the pathology

composite(p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")), p(HGNC:ZC3H14)) decreases bp(GO:locomotion) View Subject | View Object

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composite(p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")), p(HGNC:ZC3H14)) increases path(HBP:Neurodegeneration) View Subject | View Object

Appears in Networks:

composite(p(HBP:"Tau isoform E (412 aa)", var("p.Val337Met")), p(HGNC:ZC3H14)) increases p(HGNC:MAPT) View Subject | View Object

Appears in Networks:

Evidence 1beeb02876
JSON

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).

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

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Evidence 43cc35eb44
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Although a direct mechanism by which SUT-2 acts is not known, functional evidence of its binding partner ZYG-12 (122) suggests that it may act via modulating the aggresome formation by ZYG-12 (123,124).

p(HGNC:ZC3H14) regulates bp(GO:"aggresome assembly") View Subject | View Object

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Evidence 7b3fbf00ee
JSON

Comparison of the mitochondrial transport in the wildtype tau and TauA152T lines revealed striking differences; wild-type tau lines showed a late onset akin to both antero- and retrograde mitochondrial transport defects, whereas TauA152T lines showed mainly early-onset anterograde mitochondrial transport defects

p(HBP:"Tau isoform F (441 aa)") decreases bp(GO:"anterograde axonal transport of mitochondrion") View Subject | View Object

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p(HBP:"Tau isoform F (441 aa)") decreases bp(GO:"retrograde axonal transport of mitochondrion") View Subject | View Object

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p(HBP:"Tau isoform F (441 aa)", var("p.Ala152Thr")) decreases bp(GO:"anterograde axonal transport of mitochondrion") View Subject | View Object

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Evidence 662e292eab
JSON

Although the wild-type tau lines showed a mild late-onset dose-dependent Unc phenotype, TauA152T worms showed early-onset paralysis and acute neuronal dysfunction.

p(HBP:"Tau isoform F (441 aa)", var("p.Ala152Thr")) increases path(MESH:Paralysis) View Subject | View Object

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p(HBP:"Tau isoform F (441 aa)", var("p.Ala152Thr")) decreases act(a(MESH:Neurons)) View Subject | View Object

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Evidence 588be2f99d
JSON

The transgenic lines exhibited a progressive age-associated Unc phenotype, with or without phospho-mimicking mutations

p(HBP:"Tau isoform Fetal-tau (352 aa)") decreases bp(GO:locomotion) View Subject | View Object

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p(HBP:"Tau isoform Fetal-tau (352 aa)", pmod(HBP:hyperphosphorylation)) decreases bp(GO:locomotion) View Subject | View Object

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Evidence 3167744a29
JSON

Only PHP tau expression induced morphologic abnormalities in the motor neurons, but none of the lines developed substantial neurodegeneration

p(HBP:"Tau isoform Fetal-tau (352 aa)", pmod(HBP:hyperphosphorylation)) decreases a(MESH:"Motor Neurons") View Subject | View Object

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Evidence b2f0fae43f
JSON

Phosphorylation is generally increased in AD and can be recognized by diagnostic antibodies against phosphoepitopes

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

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

Appears in Networks:

Evidence dadb4b85ad
JSON

For example, AD brain tau is;4-fold more phosphorylated than normal adult brain tau(93), but a high state of phosphorylation can also occur physiologically (e.g., in fetal brain or in hibernating animals (94).

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

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

Appears in Networks:

Evidence 78d5572d2c
JSON

For example, both soluble and insoluble tau from transgenic worms generated by Kraemer and colleagues (66) was phosphorylated at most of the sites examined; however, the insoluble tau did not show reactivity at the AT8 and pS422 epitopes, which are pronounced in human AD tau.

p(HGNC:MAPT, pmod(Ph, Ser, 202)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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p(HGNC:MAPT, pmod(Ph, Ser, 422)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Thr, 205)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 422)) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Thr, 205)) View Subject | View Object

Appears in Networks:

Evidence 53a9327c01
JSON

Another MAPT polymorphism (A152T) was recently identified in patients diagnosed with progressive supranuclear palsy (PSP) (72–74).

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

Appears in Networks:

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

Appears in Networks:

Evidence 981e500ab8
JSON

Dephosphorylation of tau is achieved mainly by protein phosphatase (PP)2A, PP2B (calcineurin), and PP-1 (92).

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

Appears in Networks:

p(HGNC:PPP2CA) 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:

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.