Enhancing Heparan Sulfate 3-O-Sulfotransferase Activity to Competitively Block Tau-HSPG Interactions

h-var-6bba3e5e9a

The pathological spread of tau aggregates in Alzheimer's disease relies critically on heparan sulfate proteoglycan (HSPG)-mediated neuronal uptake, but the therapeutic approach can be redirected from sulfatase inhibition to competitive sulfation enhancement. Rather than preserving existing 6-O-sulfation patterns through SULF1/2 inhibition, this strategy leverages the competitive substrate dynamics