The Role of a Novel Topological Form of the Prion Protein in Prion Disease
Annual rept. 1 Jul 2005-30 Jun 2006
WASHINGTON UNIV ST LOUIS MO
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Mostbut not all cases of prion disease are associated with a conformationally altered form of the prion protein PrP known as PrPSc. Several lines of evidence indicate that while PrpSc is the infectious molecule, it may not be the proximate cause of toxicity in prion disease. Several other candidates for such a toxic species have been proposed, including an altered topological form of PrP known as CtmPrP. Lines of transgenic mice engineered to express CtmPrP develop a spontaneous prion-like disease. Thus, extending our knowledge of the biology of CtmPrP will likely lead to important clues about how all prion diseases induce neurotoxicity. We have also learned that CtmPrP is much less toxic when expressed on a PrP null genetic background this result has important implications for the mechanism of toxicity in prion disease. We have used this fact to determine which portions of the PrP molecule interact with CtmPrP to induce toxicity. We have also addressed the role of the Bax protein in CtmPrP-mediated neurological disease. We find that Bax is not required for the disease to develop. We have also begun to examine whether CtmPrP can be studied in a more genetically tractable system, the Bakers yeast Saccharomyces Cerevisiae.
- Anatomy and Physiology
- Medicine and Medical Research