Human prion diseases: molecular and clinical phenotypes

Human prian diseases are sporadic, acquired, and genetic neurodegenerative conditions characterized by brain accumulation and deposition of pathological prion protein. These disorders are highly heterogeneous and display a wide range of clinicopathological phenotypes. This well-known phenotypic heterogeneity is thought to be determined by two main disease modifiers: [i] the genotype at polymorphic codon 129 of the prion protein gene [PRNP], allowing three possible combinations, and [ii] the physicochemical properties of the pathological prion protein, or PrPSc, existing under distinct conformational variants. In addition to PrPSc conformation, glycosylation site occupancy of PrPSc at Asp 181 and Asp 197, and truncated PrP fragments may influence the biological properties of prion strains. Here we review molecular and clinical phenotypes encountered in human prion diseases