Journal article

Pathogenic Mutations within the Hydrophobic Domain of the Prion Protein Lead to the Formation of Protease-Sensitive Prion Species with Increased Lethality

Bradley M Coleman, Christopher F Harrison, Belinda Guo, Colin L Masters, Kevin J Barnham, Victoria A Lawson, Andrew F Hill



UNLABELLED: Prion diseases are a group of fatal and incurable neurodegenerative diseases affecting both humans and animals. The principal mechanism of these diseases involves the misfolding the host-encoded cellular prion protein, PrP(C), into the disease-associated isoform, PrP(Sc). Familial forms of human prion disease include those associated with the mutations G114V and A117V, which lie in the hydrophobic domain of PrP. Here we have studied the murine homologues (G113V and A116V) of these mutations using cell-based and animal models of prion infection. Under normal circumstances, the mutant forms of PrP(C) share similar processing, cellular localization, and physicochemical properties wi..

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Awarded by Australian Research Council

Awarded by National Health and Medical Research Council

Funding Acknowledgements

This work was supported by the Australian Research Council (FT100100560 to A. F. H.) and the National Health and Medical Research Council (628946 to A. F. H., C. L. M., and K.J.B. and 1041413 to A. F. H. and V.A.L.).