title: Scrapie associated PrP accumulation and its prevention: insights from cell culture.
abstract: Transmissible spongiform encephalopathies (TSEs), Alzheimer's disease and other amyloidoses result in the accumulation of abnormally stable, potentially amyloidogenic proteins that appear to play central roles in disease pathogenesis. Scrapie-infected tissue culture cells have become well-developed models for studying how the TSE-specific protein, protease-resistant PrP, is made from its apparently normal precursor. The conversion of PrP to the protease-resistant state occurs on the plasma membrane or along an endocytic pathway to the lysosomes. The protease-resistant PrP has a much longer half-life than normal PrP and its accumulation in lysosomes may feature in TSE pathogenesis. Congo red and certain sulfated glycans potently inhibit protease-resistant PrP formation or stabilization in cell culture. These and other observations suggest that an interaction of PrP with glycosaminoglycans is critical in protease-resistant PrP accumulation and raises the possibility that therapeutic strategies for TSEs and other amyloidoses could be based on blocking (pre)amyloid-glycosaminoglycan interactions.
authors.affiliation: Laboratory of Persistent Viral Diseases, National Institute for Allergy and Infectious Diseases, Hamilton, Montana 59840.
authors.forename: B
authors.initials: B
authors.lastname: Caughey
mesh_terms: D000818:Animals; D000998:Antiviral Agents; D002478:Cells, Cultured / Q000382:microbiology; D011328:Prions / Q000096:biosynthesis*; D012608:Scrapie / Q000382:microbiology / Q000517:prevention & control; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D011328:Prions