Role of the prion protein in human spongiform encephalopathies

The spongiform encephalopathies are a group of fatal neurodegenerative diseases that includes Creutzfeldt-Jakob disease, kuru, Gerstmann-Straussler syndrome, and fatal familial insomnia in human beings. Also called prion diseases, these disorders are unique in being both infectious and genetic in origin. Mutations in the human gene that encodes the prion protein (PrP) are strongly linked to inherited forms of the disease. The agent responsible for infectious forms of the disease is thought to be a protein called PrPSc. prp(Sc) cor responds to an altered form of the normal PrPC. Several pieces of evidence indicate that PrPSc and PrPC do not differ in their primary amino acid sequence, but rather in their conformations. Prion replication,, is believed to occur when PrPSc in the infecting inoculum interacts specifically with host PrPC, catalyzing its conversion into PrPSc. Recent in vitro studies as well as the use of transgenic animals have given new insights into the comprehension of the mechanisms of these diseases. The conversion of PrPC into PrPSc is now considered as the central event in the transmission as well as in the pathogenic process of prion diseases.