PRION DISEASES OF HUMANS AND ANIMALS

Prions cause infectious and genetic neurodegenerative diseases. Transm issible prion particles are composed largely, if not entirely, of an a bnormal isoform of the prion protein (PrPSc), which is encoded by a ch romosomal gene. A post-translational process involving a profound conf ormational change converts the cellular prion protein. (PrPC) into PrP Sc. PrPC has a high alpha-helix content and is devoid of beta-sheet; w hereas, PrPSc has a lower alpha-helix content but is high in beta-shee t. Transgenetic studies argue that a factor(s) designated protein X fu nctions in the formation of PrPSc, perhaps as a molecular chaperone. M utations in the PrP gene are genetically linked to development of neur odegeneration in humans. These mutations may cause disease by destabil izing one or more of the alpha-helices of PrPC. Investigations of prio n diseases may give insights into the more common neurodegenerative di seases.