Generating a Prion with Bacterially Expressed Recombinant Prion Protein

Abstract

Recombinant Infectious Prions Prion diseases are a group of fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in cows. The prion hypothesis states that the infectious agent of these diseases is an aberrant conformational isoform of the normal prion protein (PrP C ), a glycosylphosphatidylinositol-anchored cell surface protein enriched in the central nervous system. The final proof for the prion hypothesis is to convert bacterially expressed recombinant PrP into an infectious prion, but this has been difficult to achieve. F. Wang et al. (p. 1132 , published online 28 January; see the Perspective by Supattapone ) put recombinant PrP purified from bacteria into mice and obtained all the characteristics of the infectious agent in prion disease. The recombinant form is not only resistant to proteinase-K, but also shows infectivity in cultured cells and causes rapid disease progression in wild-type mice, yielding both the behavioral and the neuropathological symptoms.