a(CHEBI:heparin)

Entity

Name

heparin

Namespace

chebi

Namespace Version

20180906

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/chebi-names.belns

We found that internalization of tau can be efficiently competed by the presence of heparin or HS in the media (Fig. 4a) PubMed:29686391

In the case of soluble monomeric or small oligomeric tau protein, the endocytosis appears to be clathrin-dependent (reviewed in [169]). In contrast, larger aggregates of tau could bind heparin in the extracellular matrix and be internalized through macropinocytosis [170]. As a result of exocytosis and endocytosis, the spreading of tau can occur in various neurodegenerative diseases (tauopathies) including AD. Three plausible mechanisms of tau spreading are shown schematically in Figure 6. Additionally, it appea rs that microglial cells may facilitate tau propagation by phagocytosis and exocytosis of tau protein [171]. PubMed:26751493

We confirmed that heparin within the aggregated tau preparations did not contribute to tau entry into neurons, finding that uptake of both monomeric and aggregated tau was unaffected in the presence of heparin (Figures S4C and S4D PubMed:29590627

We confirmed that heparin within the aggregated tau preparations did not contribute to tau entry into neurons, finding that uptake of both monomeric and aggregated tau was unaffected in the presence of heparin (Figures S4C and S4D PubMed:29590627

We found that internalization of tau can be efficiently competed by the presence of heparin or HS in the media (Fig. 4a) PubMed:29686391

Consistent with our previous results, incubation with heparin, heparan sulfate, or 2-O-desulfated heparin reduced uptake of tau as quantified by the median 488 fluorescence intensity (Fig. 4d) PubMed:29686391

In the case of soluble monomeric or small oligomeric tau protein, the endocytosis appears to be clathrin-dependent (reviewed in [169]). In contrast, larger aggregates of tau could bind heparin in the extracellular matrix and be internalized through macropinocytosis [170]. As a result of exocytosis and endocytosis, the spreading of tau can occur in various neurodegenerative diseases (tauopathies) including AD. Three plausible mechanisms of tau spreading are shown schematically in Figure 6. Additionally, it appea rs that microglial cells may facilitate tau propagation by phagocytosis and exocytosis of tau protein [171]. PubMed:26751493

Tau contains cysteine residues in the microtubule binding region following alternative splicing of exon 10, and formation of intermolecular cysteine disulfide bonds accelerates tau aggregation. 8-Nitro-cGMP (novel second messenger of NO) exposure induced S-guanylation of tau both in vitro and in tau-overexpressed HEK293T cells. S-guanylated tau inhibited heparin-induced tau aggregation (thioflavin T). S-guanylated tau could not form tau granules and fibrils (AFM) inhibited at the step of tau oligomer formation. In P301L tau-expressing Neuro2A cells, 8-nitro-cGMP reduced the amount of sarcosyl-insoluble tau. NO-linked chemical modification on cysteine residues of tau could block tau aggregation PubMed:27601475

Heparin blocks Tau binding by masking HSPG binding sites on Tau, and sodium chlorate inhibits HSPG sulfation. PubMed:25887395

To test whether HSPGs also mediate BD Tau seeding, we titrated heparin and sodium chlorate, which inhibited seeding of all species (Fig. 8D). PubMed:25887395

After 15 min of heparin exposure, we detected low but significant amounts of seed-compe- tent monomer, and much fewer larger assemblies (Figure 6A). PubMed:29988016

After 15 min of heparin exposure, we detected low but significant amounts of seed-compe- tent monomer, and much fewer larger assemblies (Figure 6A). PubMed:29988016