Biology and Genetics of PrP Prion Strains

Cold Spring Harb Perspect Med. 2017 Aug 1;7(8):a026922. doi: 10.1101/cshperspect.a026922.


Prion diseases are a group of fatal neurodegenerative disorders caused by the misfolding of the cellular prion protein (PrPC) into a pathogenic conformation (PrPSc). PrPSc is capable of folding into multiple self-replicating prion strains that produce phenotypically distinct neurological disorders. Evidence suggests that the structural heterogeneity of PrPSc is the molecular basis of strain-specific prion properties. The self-templating of PrPSc 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Resistance
  • Humans
  • Prion Diseases / genetics*
  • Prion Diseases / metabolism*
  • Prion Diseases / pathology
  • Prion Proteins / genetics*
  • Prion Proteins / metabolism*
  • Protein Conformation
  • Protein Folding


  • Prion Proteins