Activation of Fas and caspase 3 precedes PrP accumulation in 87V scrapie

The sequence of events involved in the neurodegeneration caused by transmis sible spongiform encephalopathies is not yet known. Using a murine scrapie model in which neurodegeneration in the hippocampus is restricted to the CA 2, we show an up-regulation of the proapoptotic markers Fas and caspase 3 e arly in the incubation period prior to disease-specific prion protein (PrP) deposition and clinical signs. These results suggest that activation of Fa s and caspase 3 are involved in the early pathological sequence of events d uring murine scrapie, and that these proapoptotic markers may be a specific method for early detection of neurodegeneration. (C) 2001 Lippincott Willi ams & Wilkins.