NR AOWA
AU Luhr,K.M.; Nordström,E.K.; Löw,P.; Taraboulos,A.; Kristensson,K.
TI Cysteine proteases are involved in the processing of prion proteins
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-89
PT Konferenz-Poster
AB
The mechanisms by which protease resistant prion protein (PrPsc) is cleared from cells in the lymphoid system and/ or the CNS are not yet known. Degradation of PrPsc has lately come into focus and both macrophages and a neuroblastoma cell line (N2a) have been shown to have PrPsc degrading capacity. We have previously shown that myeloid dendritic cells have a capacity to degrade the partially protease resistant prion protein, PrPsc.
Since dendritic cells may be involved in the pathogenesis of prion infection and that they efficiently degrade PrPsc, we have used a co-culture system to study proteases involved in the degradation of PrPsc. Inhibitors of cysteine proteases inhibit the degradation of PrPsc in co-cultures of dendritic cells and scrapie infected GT1-1 cells (ScGT1-1). Treatment with the same protease inhibitors increase levels of PrPsc in ScGT1-1 cells which indicate an endogenous degradation of PrPsc in this neuronal cell type. This degradation was shown to be dependent on acidic pH, localizing this process to endosomal/ lysosomal compartments. We are now investigating the GT1-1 cell-derived cysteine proteases, comparing their expression before and during a scrapie-infection. Identifying proteases responsible for the degradation of PrPsc may be of importance for future manipulations of the uptake and spread of prions to the CNS and might elucidate mechanisms involved in clearance of PrPsc during prion infections.
Supported by EC grant QLK2-CT-2002-81628 and Stiftelsen Sigurd och Elsa Goljes minne
AD K.M. Luhr, E.K. Nordström, P. Löw, K. Kristensson, Dept. of Neuroscience, Karolinska Institutet, Stockholm, Sweden; A. Taraboulos, Dept. of Molecular Biology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
SP englisch
PO Deutschland