Séminaire LBM | Prof Chunyu Wang "Heparan Sulfate 3-O-Sulfation: A drung target...""

Heparan sulfate (HS) interacts with a number of important proteins in Alzheimer’s disease (AD), including amyloid-beta, tau and ApoE. These interactions are primarily driven by electrostatics, with specificity determined by sulfation patterns. Using NMR, SPR, glycan array and cellular studies, we have demonstrated that tau, the major component of neurofibrillary tangles, specifically recognizes the 3-O-sulfation (3-OS), a rare HS modification. In addition, ApoE, whose isoform ApoE4 is the most significant genetic risk factor for late onset AD, also interacts with 3-OS. With a novel LC-MS/MS method for quantifying 3-O-sulfation, our recent studies further demonstrate a marked increase in 3-O-sulfated HS in AD brains. These findings align with several genome-wide association studies (GWAS) where the Hs3st1 gene, encoding HS-3-O-sulfotransferase-1, is significantly linked to a heightened AD risk. Taken together, our findings underscore the significance of 3-OS in AD pathogenesis, suggesting its potential as a novel drug target and biomarker in Alzheimer’s disease.