The Role of a Novel Topological Form of the Prion Protein in Prion Disease
Abstract
Most(but 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 Baker's yeast Saccharomyces Cerevisiae.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2006
- Accession Number
- ADA470272
Entities
People
- Richard S. Stewart
Organizations
- Washington University in St. Louis