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Methods for studying prion protein (PrP) metabolism and the formation of protease-resistant PrP in cell culture and cell-free systems

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Abstract

Transmissible spongiform encephalopathies (TSE) or prion diseases result in aberrant metabolism of prion protein (PrP) and the accumulation of a protease-resistant, insoluble, and possibly infectious form of PrP, PrP-res. Studies of PrP biosynthesis, intracellular trafficking, and degradation has been studied in a variety of tissue culture cells. Pulse-chase metabolic labeling studies in scrapie-infected cells indicated that PrP-res is made posttranslationally from an apparently normal protease sensitive precursor, PrP-sen, after the latter reaches the cell surface. Cell-free reactions have provided evidence that PrP-res itself can induce the conversion of PrP-sen to PrP-res in a highly species- and strain-specific manner. These studies have shed light on the mechanism of PrP-res formation and suggest molecular bases for TSE species barrier effects and agent strain propagation.

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  1. NIH Rocky Mountain Laboratories, 903 S. 4th St., 59840, Hamilton, MT

    Byron Caughey

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  1. Byron Caughey
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  2. Gregory J. Raymond
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  3. Suzette A. Priola
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  4. David A. Kocisko
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  5. Richard E. Race
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  6. Richard A. Bessen
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  7. Peter T. Lansbury Jr.
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  8. Bruce Chesebro
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Caughey, B., Raymond, G.J., Priola, S.A. et al. Methods for studying prion protein (PrP) metabolism and the formation of protease-resistant PrP in cell culture and cell-free systems. Mol Biotechnol 13, 45–55 (1999). https://doi.org/10.1385/MB:13:1:45

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