Overview of the transmissible spongiform encephalopathies: Prion protein disorders

Abstract

The subacute transmissible spongiform encephalopathies (TSE) are a complex group of neurodegenerative disorders which includes genetic, infectious and sporadic forms exemplified by scrapie in animals and Creutzfeldt-Jakob disease in humans. An extensive mass of data indicate that the infectious agents which transmit these diseases as well as the pathogenic mechanisms leading to clinical signs are related to abnormalities of a single cellular protein, designated the prion protein (PrP). The goals of this overview are to summarize the characteristics of TSEs and of their infectious agents and to indicate how the prion hypothesis is consistent with and provides an explanation for them. Transgenic mouse studies are emphasized which verify that genetic forms of TSEs are linked to mutations in the host PrP gene and that the host species barrier to scrapie infection, scrapie incubation time and the distribution of neuropathology, which define scrapie prion isolates (‘strains’), are determined by the structure of PrP.