Prion diseases of humans and animals

Prions cause infectious and genetic neurodegenerative diseases. Transmissible prion particles are composed largely, if not entirely, of an abnormal isoform of the prion protein (PrPSc), which is encoded by a chromosomal gene. A post-translational process involving a profound conformational change converts the cellular prion protein. (PrPC) into PrPSc. PrPC has a high alpha-helix content and is devoid of beta-sheet; whereas, PrPSc has a lower alpha-helix content but is high in beta-sheet. Transgenetic studies argue that a factor(s) designated protein X functions in the formation of PrPSc, perhaps as a molecular chaperone. Mutations in the PrP gene are genetically linked to development of neurodegeneration in humans. These mutations may cause disease by destabilizing one or more of the alpha-helices of PrPC. Investigations of prion diseases may give insights into the more common neurodegenerative diseases.