Braun
Fakultäten » Medizinische Fakultät » Neuropathologie, Institut für » Prof. Dr. Adriano Aguzzi » Braun
Completed research project
| Title / Titel | Elucidation of the physiological function of the prion protein | ||||
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| Abstract (PDF, 14 KB) | |||||
| Summary / Zusammenfassung | The physiological function of the prion protein PrPC that is highly expressed in the brain is still not known. Prnp knock-out mice showed no obvious developmental defect that could be exploited to understand PrPC function. However, PrPC is indispensable for the acquisition or the replication of scrapie. The laboratory of Charles Weissmann in collaboration with our group found that transgenic expression of an amino-truncated PrPC mutant causes early-onset ataxia associated with cerebellar granule cell degeneration and death at two to three months of age in PrPC deficient mice. Also Doppel (Dpl) , a recently detected PrPC homologue, causes neurodegeneration in the cerebellum when overexpressed in PrPC deficient mice. Its structure resembles the neurotoxic, amino proximally truncated PrP. The similarity of the phenotypes observed in Dpl and DPrP overexpressing mice and the structural resemblance between the two proteins suggest that they act by means of similar mechanisms to induce cell death. To gain insight into the mechanisms of Dpl and DPrP induced neurotoxicity, we intend to establish an in vitro model that is amenable to genetic and biochemical analysis. An understanding of these mechanisms might reveal the physiological function of PrPC. |
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| Keywords / Suchbegriffe | Prion protein, truncated prion protein, Doppel, neurodegeneration, in vitro model | ||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Other links to external web pages | http://www.neuropathologie.usz.ch/ | ||||
| Funding source(s) / Unterstützt durch |
SNF (Personen- und Projektförderung) |
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| Duration of Project / Projektdauer | Apr 2001 to Mar 2004 |