Molecular Distinction between Pathogenic and Infectious Properties of the Prion Protein
AUTOR(ES)
Chiesa, Roberto
FONTE
American Society for Microbiology
RESUMO
Tg(PG14) mice express a prion protein (PrP) with a nine-octapeptide insertion associated with a human familial prion disease. These animals spontaneously develop a fatal neurodegenerative disorder characterized by ataxia, neuronal apoptosis, and accumulation in the brain of an aggregated and weakly protease-resistant form of mutant PrP (designated PG14spon). Brain homogenates from Tg(PG14) mice fail to transmit disease after intracerebral inoculation into recipient mice, indicating that PG14spon, although pathogenic, is distinct from PrPSc, the infectious form of PrP. In contrast, inoculation of Tg(PG14) mice with exogenous prions of the RML strain induces accumulation of PG14RML, a PrPSc form of the mutant protein that is infectious and highly protease resistant. Like PrPSc, both PG14spon and PG14RML display conformationally masked epitopes in the central and octapeptide repeat regions. However, these two forms differ profoundly in their oligomeric states, with PG14RML aggregates being much larger and more resistant to dissociation. Our analysis provides new molecular insight into an emerging puzzle in prion biology, the discrepancy between the infectious and neurotoxic properties of PrP.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=164780Documentos Relacionados
- Glycosylation differences between the normal and pathogenic prion protein isoforms
- The consequences of pathogenic mutations to the human prion protein
- Amyloid aggregates of the HET-s prion protein are infectious
- Effect of silica on the pathogenic distinction between herpes simplex virus type 1 and 2 hepatitis in mice.
- Location and properties of metal-binding sites on the human prion protein
