Genoud
Fakultäten » Medizinische Fakultät » Neuropathologie, Institut für » Prof. Dr. Adriano Aguzzi » Genoud
Completed research project
| Title / Titel | Block of prion replication by a soluble dimeric form of PrP | ||||
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| Abstract (PDF, 14 KB) | |||||
| Summary / Zusammenfassung | Conversion of cellular prion protein (PrPC) into a pathological conformer (PrPSc) is thought to be promoted by PrPSc in a poorly understood process. We have generated transgenic mice expressing a soluble dimeric PrPC fused to immunoglobulin Fcg (PrP-Fc2): PrP-Fc2 delays onset of disease, PrPSc accumulation, and agent replication following prion infection. In infected PrP-expressing brains, PrP-Fc2 relocates to lipid rafts and associates with PrPSc, without acquiring protease resistance. Accordingly, mice expressing PrP-Fc2, but lacking endogenous PrPC, are resistant to scrapie, do not accumulate PrP-Fc2Sc, and do not transmit disease to others. The unique properties of PrP-Fc2 suggest that soluble PrP derivatives may represent a new class of prion replication antagonists. We are using different techniques to assess the antiprion property of soluble dimeric PrP. | ||||
| Publications / Publikationen | Meier, P., Genoud, N., Prinz, M., Maissen, M., Rulicke, T., Zurbriggen, A., Raeber, A. J., and Aguzzi, A. (2003). Soluble Dimeric Prion Protein Binds PrP(Sc) In Vivo and Antagonizes Prion Disease. Cell 113, 49-60 | ||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
Foundation Bety and David Koetser Foundation |
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| Duration of Project / Projektdauer | Jan 2001 to Dec 2004 |