Abstract
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 the studies of the past 40 years 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 PrP(Sc), are essential in determining prion fate in an organism. The current extra-view article discusses recent advancements on the role of N-linked glycans and specifically their sialylation status in controlling prion fate. In addition, this manuscript introduces a new concept on the important role of strain-specific functional carbohydrate epitopes on the PrP(Sc) surface as main determinants of strain-specific biologic features. According to this concept, individual strain-specific folding patterns of PrP(Sc) govern selection of PrP(C) sialoglycoforms expressed by a host that can be accommodated within particular PrP(Sc) structures. Strain-specific patterns of functional carbohydrate epitopes formed by N-linked glycans on PrP(Sc) surfaces define strain-specific biologic features. As a constitutive part of PrP(Sc), the individual strain-specific patterns of carbohydrate epitopes propagate faithfully within a given host as long as individual strain-specific PrP(Sc) structures are maintained, ensuring inheritance of strain-specific biologic features.