Activation of Fas and caspase 3 precedes PrP accumulation in 87V scrapie.
The sequence of events involved in the neurodegeneration caused by transmissible spongiform encephalopathies is not yet known. Using a murine scrapie model in which neurodegeneration in the hippocampus is restricted to the CA2, we show an up-regulation of the proapoptotic markers Fas and caspase 3 early in the incubation period prior to disease-specific prion protein (PrP) deposition and clinical signs. These results suggest that activation of Fas and caspase 3 are involved in the early pathological sequence of events during murine scrapie, and that these proapoptotic markers may be a specific method for early detection of neurodegeneration.
Jamieson
E
E
Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, UK.
Jeffrey
M
M
Ironside
J W
JW
Fraser
J R
JR
D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D011328:Prions / Q000378:metabolism*; D012608:Scrapie / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology; D019014:fas Receptor / Q000096:biosynthesis / Q000378:metabolism*
D011328:Prions; D019014:fas Receptor; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases