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 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. We have attempted to establish a cell culture model for CtmPrP-dependent toxicity to further define the mechanism of cell injury.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2005
- Accession Number
- ADA462482
Entities
People
- Richard S. Stewart
Organizations
- Washington University in St. Louis