NR APAR
AU Yadavalli,R.; Guttmann,R.P.; Centers,A.P.; Seward,T.; Williamson,A.; Telling,G.C.
TI Prion propagation is a calpain-dependent process
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Oral sessions OS-37
PT Konferenz-Vortrag
AB PrPc and PrPsc are subject to diverse proteolytic processing events but their significance in prion pathogenesis has not been fully explored. Here we describe that the endoproteolytic cleavage of PrPsc by calpain, a calcium (Ca2+) -activated cysteine protease, is a central event in the conversion of PrPc to PrPsc and prion propagation. While increases in intracellular Ca2+ stimulate PrPsc cleavage, prevention of PrPsc proteolysis by pharmacological inhibitors of calpain, or overexpression of calpastatin, the endogenous inhibitor of calpain, result in reduced PrPsc accumulation and prion titer suggesting that the calpain-cleaved fragment of PrPsc, designated C2, facilitates the conversion of PrPc to the pathogenic conformation. Our observations shed new light on the mechanism of prion propagation involving cleavage of PrPsc by calpain.
AD Rajgopal Yadavalli, Rodney P. Guttmann, Adrian P. Centers, Tanya Seward, Glenn C. Telling, Sanders Brown Center on Aging, University of Kentucky, USA; Glenn C. Telling, Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, USA; Rodney P. Guttmann, Department of Physiology, University of Kentucky, USA; Glenn C. Telling, Department of Neurology, University of Kentucky, USA; Anthony Williamson, Department of Immunology, Scripps Research Institute, USA
SP englisch
PO Deutschland