Biology and Genetics of PrP Prion Strains

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.