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Published on: November 19, 2010
Anti-LRP/LR antibody W3 hampers peripheral PrPSc propagation in scrapie infected mice
Chantal Zuber1, Gerda Mitteregger, Claudia Pace
1Laboratorium für Molekulare Biologie-Genzentrum, Institut für Biochemie der Ludwig-Maximilians-Universitat München, München, Germany.
Abstract:
We identified the 37kDa/67kDa laminin receptor (LRP/LR) as a cell surface receptor for the cellular prion protein (PrP(c)) and the infectious prion protein (PrP(Sc)). Recently, we showed that anti-LRP/LR antibody W3 cured scrapie infected N2a cells. Here, we demonstrate that W3 delivered by passive immunotransfer into C57BL/6 mice reduced the PrP(Sc) content in the spleen significantly by 66%, demonstrating an impairment of the peripheral PrP(Sc) propagation. In addition, we observed a 1.8-fold increase in survival of anti-LRP/LR antibody W3 treated mice (mean survival of 31 days) compared to preimmune serum treated control animals (mean survival of 17 days). We conclude that the significant effect of anti-LRP/LR antibody W3 on the reduction of peripheral PrP(Sc) propagation might be due to the blockage of the prion receptor LRP/LR which is required, as previously shown in vitro, for PrP(Sc) propagation in vivo.
Insights
An antibody targeting the laminin receptor (LRP/LR) significantly reduced prion protein (PrPSc) in mice, extending survival. This suggests LRP/LR blockage impairs peripheral prion propagation.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- The 37kDa/67kDa laminin receptor (LRP/LR) is identified as a cell surface receptor for both cellular prion protein (PrPc) and infectious prion protein (PrPSc).
- Previous in vitro studies demonstrated that an anti-LRP/LR antibody (W3) could cure scrapie-infected N2a cells.
Purpose of the Study:
- To investigate the in vivo efficacy of anti-LRP/LR antibody W3 in reducing peripheral prion propagation and improving survival in a mouse model.
- To assess the impact of blocking LRP/LR on PrPSc levels and disease progression.
Main Methods:
- Passive immunotransfer of anti-LRP/LR antibody W3 into C57BL/6 mice infected with prions.
- Quantification of PrPSc content in spleen tissue.
- Monitoring and comparison of survival rates between treated and control groups.
Main Results:
- Passive immunotransfer of W3 significantly reduced splenic PrPSc content by 66%.
- Treated mice exhibited a 1.8-fold increase in mean survival (31 days) compared to controls (17 days).
- Demonstrated impairment of peripheral PrPSc propagation in vivo.
Conclusions:
- The anti-LRP/LR antibody W3 effectively reduces peripheral PrPSc propagation in vivo.
- Blocking the LRP/LR receptor is a potential therapeutic strategy for prion diseases.
- LRP/LR plays a crucial role in the in vivo propagation of PrPSc.
