Human prion disease and human prion protein disease.

Abstract

Creutzfeldt-Jakob disease (CJD), kuru, and Gerstmann-Sträussler syndrome (GSS) show clinical and pathological characteristics similar to those of scrapie, a transmissible neurodegenerative disease of sheep and goats. These diseases are caused by slow infectious agents designated as prions (PRUSINER 1982). The major component of prions is prion protein (PrP; MCKINLEY et al. 1983), which is encoded in normal human genomes located on the short arm of chromosome 20 (SPARKES et al. 1986). In 1989 codon 102 or codon 117 point mutations of human PrP were reported to be linked to GSS (HSIAO et al. 1989; DOH-URA et al. 1989). The results in codon 102 transgenic mice also strengthen the idea that this mutation is one of the essential events that cause GSS (HSIAO etal. 1990). The several polymorphisms or mutations were also reported in familial CJD and familial dementia (GOLDGARBER et al. 1989; GOLDFARB et al. 1991; MEDORI et al. 1992; KITAMOTO et al. 1993a,b).