The Role of a Novel Topological Form of a Prion Protein in Prion Disease
Abstract
Prion diseases are fatal neurological disorders of humans and other mammals. Prion diseases show an unusual etiology: they can arise from genetically, from infection through prion-contaminated food products, or sporadically. 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 (including lines described in this proposal). Thus, extending our knowledge of the biology of CtmPrP will likely lead to important clues about how all prion diseases induce neurotoxicity. We have characterized the cell biology of CtmPrP in detail in cultured neurons, and show that its cellular trafficking differs from normal PrP. 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA430363
Entities
People
- Richard S. Stewart
Organizations
- Washington University in St. Louis