a(HBP:"6-O-sulfated heparin")

Entity

Name

6-O-sulfated heparin

Namespace

HBP

Namespace Version

20181128

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/7e4be528f12abd28be768b62402fba6e083eaf9e/export/hbp-names.belns

These results were consistent when tested in iPS-derived neurons (Fig. 4b), demonstrating that the 6-O-sulfation motif is indeed a critical determinant for cellular tau entry PubMed:29686391

Removal of N-sulfates or 2-O-sulfates had little effect on tau binding (15.0 ± 5 nM and 7.4 ± 1.0 nM, respectively), while removal of all O-sulfates and, in particular 6-O-sulfates, led to a significant decrease in tau binding (>1 μM in each case; Fig. 3c,d) PubMed:29686391

Previous reports had indicated that internalization of tau could be regulated by HSPGs16, but our identification of HS6ST1, an enzyme that is responsible for 6-O-sulfation of HSPGs, supports a hypothesis that specific motifs on HSPGs might be important for tau uptake PubMed:29686391

Overexpression of the constructs was confirmed with immunocytochemistry and qPCR analysis (Fig. 4f and Supplementary Fig. 3d) and the ability of the enzymes to reduce 6-O sulfation on the cell surface was confirmed by HPLC (Supplementary Fig. 3e,f) PubMed:29686391

Overexpression of the constructs was confirmed with immunocytochemistry and qPCR analysis (Fig. 4f and Supplementary Fig. 3d) and the ability of the enzymes to reduce 6-O sulfation on the cell surface was confirmed by HPLC (Supplementary Fig. 3e,f) PubMed:29686391

Removal of N-sulfates or 2-O-sulfates had little effect on tau binding (15.0 ± 5 nM and 7.4 ± 1.0 nM, respectively), while removal of all O-sulfates and, in particular 6-O-sulfates, led to a significant decrease in tau binding (>1 μM in each case; Fig. 3c,d) PubMed:29686391

Likewise, addition of 2-O-desulfated heparin was able to reduce uptake, whereas 6-O-desulfated heparin or chondroitin sulfate (negative control) were significantly less effective at reducing uptake (Fig. 4a) PubMed:29686391

These results were consistent when tested in iPS-derived neurons (Fig. 4b), demonstrating that the 6-O-sulfation motif is indeed a critical determinant for cellular tau entry PubMed:29686391

Chondroitin sulfate and 6-O-desulfated heparin incubation did not reduce the median fluorescence, verifying that 6-O-sulfation is also important for tau internalization ex vivo (Fig. 4d and Supplementary Fig. 3b) PubMed:29686391