NR ATHU
AU Mitteregger,G.; Krebs,B.; Xiang,W.; Nölting,S.; Kohlmannsperger,V.; Vosko,M.; Hamann,G.F.; Kretzschmar,H.A.
TI The octarepeat region is required for the neuroprotective function of the cellular prion protein PrPc
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Cell Biology of PrPc and PrPsc CELL-26
PT Konferenz-Poster
AB The cellular prion protein (PrPc) seems to play a fundamental role in neuroprotection and oxidative stress reaction. The mechanisms appear to involve copper binding to the N-terminal coctarepeat region of PrPc, and cell signalling by the PI3K/Akt pathway. To investigate the role of the octarepeat in vivo we used transgenic C4 mice that lack the octarepeat (PrPdelta32-93) and subjected them to controlled ischemia. In ischemic brains we found increased synthesis of PrP mRNA in wildtype mice and an increased degradation of PrPc. The infarct size in Prnp-/- animals was increased threefold when compared to wildtype animals. The infarct size in C4 animals was identical to Prnp-/- mice. The C4 protein therefore does not functionally rescue the Prnp-/- phenotype. It is quite clear that the N-terminal copper binding octarepeat has a lead function in PrPc physiology and neuroprotection against oxidative stress in vivo.
AD G.Mitteregger, B.Krebs, W.Xiang, S.Nölting, V.Kohlmannsperger, H.A.Kretzschmar, Center for Neuropathology and Prion Research, LMU Munich, Germany; M.Vosko, G.F.Hamann, Department of Neurology, Klinikum Grosshadern, LMU Munich, Germany
SP englisch
PO Deutschland