Chemistry and Molecular Biology of Transmissible Spongiform Encephalopathies

Abstract Prion diseases are currently in the spotlight. Among them, the Creutzfeldt–Jakob disease in humans, scrapie in sheep, and bovine spongiform encephalopathy, or mad cow disease, are most commonly known. The term “spongiform” refers to the characteristic appearance of the lesions found in affected brains. It is likely that prion diseases originate from a causative agent that replicates independently of nucleic acids. Current research assumes that a structural isoform of prion protein, the scrapie form PrPSc, is the responsible pathogen. The three‐dimensional structure, but not the amino acid sequence of the isoform differs from that of the normal cellular isoform, PrPc. According to a widely accepted hypothesis, the normal isoform of the protein is converted by an autocatalytic process into the scrapie form upon contact with the latter. This hypothesis has not yet been proven. However, considerable progress has been made in the last few years, which might provide answers to many open questions about prion diseases, the subject of this review.