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a(HBP:"Tau fibrils")

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Entity

Name
Tau fibrils
Namespace
HBP
Namespace Version
20181119
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/90e1cb9e5e882703380c9db8d4915ac6f3cba137/export/hbp-names.belns

Appears in Networks 11

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

Extracellular Monomeric and Aggregated Tau Efficiently Enter Human Neurons through Overlapping but Distinct Pathways v1.0.1

TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading v1.0.0

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

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

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

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

Tau oligomers and tau toxicity in neurodegenerative disease v1.0.0

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

Inhibition of tau aggregation in a novel Caenorhabditis elegans model of tauopathy mitigates proteotoxicity v1.0.0

Extracellular low-n oligomers of tau cause selective synaptotoxicity without affecting cell viability v1.0.0

Tau Trimers Are the Minimal Propagation Unit Spontaneously Internalized to Seed Intracellular Aggregation v1.0.0

Tau in physiology and pathology v1.0.0

In-Edges 19

act(p(HGNC:HTRA1)) increases deg(a(HBP:"Tau fibrils")) View Subject | View Object

Tubulin was later identified as a substrate for HTRA1, suggesting HTRA1 may be involved in mediating microtubule function (42, 43). A more recent study showed that HTRA1 can cleave recombinant tau in vitro into multiple fragments of varying sizes, and furthermore can degrade insoluble and fibrillarized tau (16). PubMed:24027553

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Annotations
Text Location
Review

bp(GO:"actin filament polymerization") increases tloc(a(HBP:"Tau fibrils"), fromLoc(GO:"extracellular region"), toLoc(MESH:Neurons)) View Subject | View Object

Disruption of actin polymerization has previously been shown to inhibit entry of fibrils formed of the tau repeat domain (Holmes et al., 2013) PubMed:29590627

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act(a(MESH:Astrocytes)) increases a(HBP:"Tau fibrils") View Subject | View Object

In addition, flow cytometry analysis demonstrated that heparin reduces dye-conjugated pff uptake in both TFEB and EGFP transduced astrocytes, suggesting that macropino- cytosis is responsible for astroglial pff uptake PubMed:30108137

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Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) increases a(HBP:"Tau fibrils") View Subject | View Object

Our results demonstrate a statistically significant increase of 12% in the uptake of pffs in TFEB transduced astrocytes relative to control at the 1-h time point, with a 22% relative increase in up- take in the TFEB transduced cells at 4 h PubMed:30108137

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Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) increases a(HBP:"Tau fibrils") View Subject | View Object

Flow cytometry revealed that Torin1 treatment of TFEB transduced astrocytes increased dye-conjugated pff uptake 63% relative to EGFP transduced controls as shown by median fluorescence in- tensity, while under basal conditions, the TFEB overexpressing astrocytes increased uptake just 18% relative to EGFP expressing controls (Fig. 2 K). Thus, TFEB enhances phagocytic pathways in astrocytes, in particular increasing the uptake of pffs. PubMed:30108137

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Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) increases a(HBP:"Tau fibrils") View Subject | View Object

. Recapitulating the uptake assay with dye-conjugated pffs in TFEB KO astrocytes, we observed a modest reduction pff uptake compared with primary astrocytes from littermate controls PubMed:30108137

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Annotations
Cell Ontology (CL)
astrocyte

p(MGI:Tfeb) increases tloc(a(HBP:"Tau fibrils")) View Subject | View Object

In sum, these data suggest that TFEB stimulates uptake and trafficking of pffs to the lysosome for degradation. PubMed:30108137

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Annotations
Cell Ontology (CL)
astrocyte

a(HBP:"Tau fibrils") causesNoChange tloc(a(HBP:"Tau fibrils"), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Further, human iPS-derived neurons also showed a preference for smaller structures of tau, with fibrillized tau showing nearly no uptake (Fig. 1d) PubMed:29686391

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Annotations
MeSH
Neurons

a(HBP:"granular tau oligomers") increases a(HBP:"Tau fibrils") View Subject | View Object

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

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Annotations
Confidence
Medium
MeSH
Cerebral Cortex

a(MESH:"Heparan Sulfate Proteoglycans") increases a(HBP:"Tau fibrils") View Subject | View Object

Consistently, HSPGs have been implicated in amyloid as well as tau fibril formation in vitro, presumably facilitated by anionic moieties PubMed:28420982

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

p(HGNC:PPID) decreases a(HBP:"Tau fibrils") View Subject | View Object

CyP40 was recently shown to disaggregate tau fibrils in vitro and prevents toxic tau accumulation in vivo preserving memory, demonstrating a neuroprotective role for CyP40 in the brain (Baker et al., 2017). PubMed:29311797

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a(HBP:"Tau aggregates") hasComponent a(HBP:"Tau fibrils") View Subject | View Object

Appears in Networks:

a(HBP:cmp16) decreases a(HBP:"Tau fibrils") View Subject | View Object

We next analysed the most prominent Tau aggregation inhibitor compound from a recent- ly published in vitro screen (compound #16 in reference 33), which belongs to the ATPZ class of Tau inhibitors (5-amino-3-(4-chlorophenyl)-N-cyclopropyl-4-oxo-3,4-dihyd- rothieno[3,4- D ]pyridazine-1-carboxamide, referred to as cmp16 for simplicity, structure shown in Fig. 9A). This com- pound prevents Tau fibril formation in vitro, and is able to cross the mammalian blood–brain barrier, an attribute that makes it favourable for clinical applications (33). PubMed:22611162

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p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) increases a(HBP:"Tau fibrils") View Subject | View Object

TauRDΔK comprises the structural elements required for the pathologic assembly of tau filaments, and it causes reversible memory deficits and synapse loss in regulatable transgenic mice [11,25]. PubMed:28528849

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complex(a(HBP:"Tau fibrils"), p(HGNCGENEFAMILY:Syndecans)) hasComponent a(HBP:"Tau fibrils") View Subject | View Object

Appears in Networks:

complex(a(HBP:"Tau fibrils"), p(HGNCGENEFAMILY:Syndecans)) increases tloc(a(HBP:"Tau fibrils"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

Heparan sulfate proteoglycans (HSPGs) are cell surface pro- teins that bind Tau fibrils and are required for their uptake and seeding (10). PubMed:25887395

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complex(p(HGNC:MAPT), p(HGNC:MAPT), p(HGNC:MAPT)) increases tloc(a(HBP:"Tau fibrils"), fromLoc(MESH:"Extracellular Space"), toLoc(MESH:"Intracellular Space")) View Subject | View Object

Within the limits of our detection, neither monomer nor dimer was internalized (Fig. 5, A and B). By contrast, trimers and larger species were readily internalized, with trimer uptake being slightly less efficient (Fig. 5, A and B). We did not observe an upper limit of size in terms of uptake. PubMed:25887395

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p(HGNC:MAPT, frag("243_375")) increases a(HBP:"Tau fibrils") View Subject | View Object

Tau RD fibrillizes very efficiently in vitro, making it ideal for fundamental studies (13). PubMed:25887395

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

The motif VQIVYK has been shown to be sufficient to form fibrils composed of steric ‘zippers’ formed by two tightly interdigitated β‑sheets. PubMed:26631930

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Out-Edges 3

a(HBP:"Tau fibrils") causesNoChange tloc(a(HBP:"Tau fibrils"), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Further, human iPS-derived neurons also showed a preference for smaller structures of tau, with fibrillized tau showing nearly no uptake (Fig. 1d) PubMed:29686391

Appears in Networks:
Annotations
MeSH
Neurons

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

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

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

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

The fibril-treated cells (cross-linked with GA or not) did not reduce the spine density significantly (Fig 4C, bars 8 and 9). PubMed:28528849

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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.