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- W2034609928 abstract "The prion hypothesis proposes that the agent responsible for the neurodegenerative diseases of scrapie, CJD and BSE is a disease-causing isoform of the prion protein termed PrPSc. The experimental evidence that the prion protein and PrP gene is central to all aspects of the disease is substantial with the exception of the phenomenon of strains. Studies on the passage of scrapie isolates in genetically inbred mice have demonstrated reproducible variation in the incubation period and pathology. This requires that the prion agent carry a heritable informational molecule (conventionally nucleic acid). If the prion hypothesis is correct, it must explain strains. Recently, limited evidence has begun to emerge that the phenotypic variation observed in scrapie strains may be due to multiple conformations of PrPSc. This paper demonstrates that eight different prion strain passages in hamsters can be distinguished by the use of a conformation-dependent immunoassay. The assay relies on the observation that the binding of antibodies to PrPSc is weak unless the molecule is denatured. The ratio of antibody binding to native and denatured brain extracts from hamsters infected with different strains combined with the concentration of prion protein present gives a unique profile for each strain. Using this assay, Safar et al.1 Safar J. et al. Eight prion strains have PrPSc molecules with different conformations. Nat. Med. 1998; 4: 1157-1165 Crossref PubMed Scopus (1059) Google Scholar have also correlated the incubation time of various strains with the relative amounts of protease-sensitive PrPSc and suggest that the rate of clearance of PrPSc rather than the rate of its synthesis within a cell determines the ultimate incubation period of the disease. Whether the variation in conformation of PrPSc and differences in the clearance rates of PrPSc can also explain the neuropathological variations associated with strains remains to be seen." @default.
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- W2034609928 date "1999-01-01" @default.
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- W2034609928 title "Prions – what a strain..." @default.
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- W2034609928 doi "https://doi.org/10.1016/s0168-9525(98)01685-0" @default.
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