The 37 kDa/67 kDa laminin receptor is required for PrP(Sc) propagation in scrapie-infected neuronal cells |
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Authors: | Leucht Christoph Simoneau Steve Rey Clémence Vana Karen Rieger Roman Lasmézas Corinne Ida Weiss Stefan |
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Affiliation: | Christoph Leucht, Steve Simoneau, Clémence Rey, Karen Vana, Roman Rieger, Corinne Ida Lasmézas, and Stefan Weiss |
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Abstract: | The accumulation of PrPSc in scrapie-infected neuronal cells has been prevented by three approaches: (i) transfection of ScMNB cells with an antisense laminin receptor precursor (LRP) RNA-expression plasmid, (ii) transfection of ScN2a cells and ScGT1 cells with small interfering RNAs (siRNAs) specific for the LRP mRNA, and (iii) incubation of ScN2a cells with an anti-LRP/LR antibody. LRP antisense RNA and LRP siRNAs reduced LRP/LR expression and inhibited the accumulation of PrPSc in these cells. The treatments also reduced PrPc levels. The anti-LRP/LR antibody, W3, abolished PrPSc accumulation and reduced PrPc levels after seven days of incubation. Cells remained free of PrPSc after being cultured for 14 additional days without the antibody, whereas the PrPc level was restored. Our results demonstrate the necessity of the laminin receptor (LRP/LR) for PrPSc propagation in cultured cells and suggest that LRP/LR-specific antibodies could be used as powerful therapeutic tools in the treatment of transmissible spongiform encephalopathies. |
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