Prion protein conversions: insight into mechanisms, TSE transmission barriers and strains.
Conversion of PrP(C) to aberrant forms such as PrP(Sc) appears to be critical in the transmission and pathogenesis of transmissible spongiform encephalopathies (TSEs) or prion diseases. In vitro studies have shown that TSE-associated, protease-resistant forms of PrP can cause PrP(C) to convert to forms that are similarly protease-resistant under a wide variety of conditions. These observations have provided evidence that pathological forms of PrP have at least limited capacity to propagate themselves, which is necessary for them to be infectious. PrP conversion reactions have proven to be highly specific and appear to account, at least in part, for TSE species barriers and the propagation of strains. Such in vitro conversion systems have yielded insights into the molecular mechanisms of TSE disease and are being exploited as screens for anti-TSE drugs and as bases for diagnostic tests.
Caughey
Byron
B
NIAID Rocky Mountain Laboratories, NIH, Hamilton, Montana 59840, USA.
D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D004198:Disease Susceptibility; D016643:Encephalopathy, Bovine Spongiform / Q000378:metabolism / Q000635:transmission*; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D011108:Polymers; D018620:PrPSc Proteins / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
D011108:Polymers; D018620:PrPSc Proteins; D011328:Prions; D010450:Endopeptidases