TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

Scrapie, bovine spongiform encephalopathy (BSE), and the Creutzfeldt-J akob disease (CJD) belong to a group of lethal neurodegenerative disor ders in mammals. Prion diseases or transmissible spongiform encephalop athies (TSEs) are characterized by the accumulation of an abnormal iso form (PrPSc) of the host-encoded cellular prion protein (PrPC) in the brain. The infectious agent, the 'prion,' is believed to be devoid of informational nucleic acid and to consist largely, if not entirely, of PrPSc. The PrP isoforms contain identical amino acid sequences yet di ffer in their overall secondary structure with the PrPSc isoform posse ssing a higher beta-sheet and lower alpha-helix content than PrPC. Elu cidation of the three-dimensional structure of PrPC has provided impor tant clues on the molecular basis of inherited human TSEs and on the s pecies barrier phenomenon of TSEs. Nevertheless, the molecular mechani sm of the conformational rearrangement of PrPC into PrPSc is still unk nown, mainly due to the lack of detailed structural information on PrP Sc. Within the framework of the 'protein only' hypothesis, two plausib le models for the self-replication of prions have been suggested, the conformational model and the nucleation-dependent polymerization model . (C) 1998 Academic Press.