Abstract
Prion diseases display multiple disease phenotypes characterized by diverse clinical symptoms, different brain regions affected by the disease, distinct cell tropism and diverse PrP(Sc) deposition patterns. The diversity of disease phenotypes within the same host is attributed to the ability of PrP(C) to acquire multiple, alternative, conformationally distinct, self-replicating PrP(Sc) states referred to as prion strains or subtypes. Structural diversity of PrP(Sc) strains has been well documented, yet the question of how different PrP(Sc) structures elicit multiple disease phenotypes remains poorly understood. The current article reviews emerging evidence suggesting that carbohydrates in the form of sialylated N-linked glycans, which are a constitutive part of PrP(Sc), are important players in defining strain-specific structures and disease phenotypes. This article introduces a new hypothesis, according to which individual strain-specific PrP(Sc) structures govern selection of PrP(C) sialoglycoforms that form strain-specific patterns of carbohydrate epitopes on PrP(Sc) surface and contribute to defining the disease phenotype and outcomes.