NR AXVB
AU Reissinger,A.; Wagner,W.; Hamman,J.; Mehlhase,J.; Löwer,J.; Montrasio,F.
TI Involvement of the Heat Shock Cognate Protein 70 in Protection of Mouse Neuroblastoma Cells from Cytosolic Prion Protein-mediated Cytotoxicity
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.74
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
The molecular mechanisms of prion-mediated neurodegeneration are not yet fully understood. Recent in vitro and in vivo data indicated that neuronal death might be triggered by cytosolic accumulation of misfolded cellular prion protein (PrPc) due to impairment of proteasomal degradation of misfolded PrPc molecules. Approximately 10% of PrPc is misfolded, recognized by the endoplasmic reticulum and retrotranslocated to the cytoplasm for degradation by the proteasome. However, contradicting results on cytosolic PrP (Cy-PrP)-mediated neurotoxicity in cultured cells have been reported.
To investigate Cy-PrP-mediated effects in cultured cells, we transfected mouse neuroblastoma cells (N2a) with Cy-PrP and determined cytotoxicity using several assays. We found that Cy-PrP expression was not sufficient to trigger cytotoxicity in N2a cells and that Cy-PrP accumulated in fine foci and colocalized with the heat shock cognate protein 70 (Hsc 70).
Since molecular chaperones have been suggested to play an important protective role in PrP-mediated pathogenesis, our interest focused on the effects of a specific Hsc 70 siRNA-mediated knock-down on Cy-PrP-mediated cytotoxicity.
Our results will reveal if the Cy-PrP-mediated toxic phenotype can be rescued by knocking down the putative cytoprotective element.
AD A. Reissinger, W. Wagner, J. Hamman, J. Mehlhase, J. Löwer, F. Montrasio, Paul-Ehrlich-Institute, Prion Research Group, Germany
SP englisch
PO Schottland
EA pdf-Datei und Poster (Postertitel: Protective Role of the Molecular Chaperone Hsc 70 in Cytosolic Prion Protein-Induced Neurotoxicity)