Biology and Genetics of PrP Prion Strains

Abstract

Prion diseases are a group of fatal neurodegenerative disorders caused by the misfolding of the cellular prion protein (PrP^C) into a pathogenic conformation (PrP^Sc). PrP^Sc is capable of folding into multiple self-replicating prion strains that produce phenotypically distinct neurological disorders. Evidence suggests that the structural heterogeneity of PrP^Sc is the molecular basis of strain-specific prion properties. The self-templating of PrP^Sc typically ensures that prion strains breed true upon passage. However, prion strains also have the capacity to conformationally transform to maximize their rate of replication in a given environment. Here, we provide an overview of the prion-strain phenomenon and describe the role of strain adaptation in drug resistance. We also describe recent evidence that shows the presence of distinct conformational strains in other neurodegenerative disorders.