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Appears in Networks 11

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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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.