Prion protein misfolding and prion diseases: beyond protein-centric view

Among a broad range of hypotheses on the molecular nature of transmissible spongiform encephalopathy or scrapie agents discussed in 1960s was a hypothesis of self‐replicating polysaccharides. While a number of studies of the past 40 years, including the studies from our laboratory, provided unambiguous proof that this is not the case, emerging evidence suggests that carbohydrates in the form of sialylated N‐linked glycans, which are a constitutive part of mammalian prions or PrPSc, are essential in determining prion fate in an organism. Our most recent work uncovered the role of N‐linked glycans and specifically their sialylation status in controlling prion fate. The seminar will provide an overview of our recent work on the role of N‐linked glycans and introduce a new concept that carbohydrate epitopes on the PrPSc surface serve as main determinants of strain‐specific biologic features.