Prion diseases of humans and animals

Abstract 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. PrPChas a high α-helix content and is devoid of β-sheet; whereas, PrPSchas a lower α-helix content but is high in β-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 α-helices of PrPC. Investigations of prion diseases may give insights into the more common neurodegenerative diseases.