Prion disease is the only naturally occurring infectious protein misfolding disorder. The chemical nature of the infectious agent has been debated for more than half a century. Early studies on scrapie suggested that the unusual infectious agent might propagate in the absence of nucleic acid. The ‘protein-only hypothesis’ provides a theoretical model to explain how a protein self-replicates without nucleic acid, which predicts that a prion, the proteinaceous infectious agent, propagates by converting its normal counterpart into the likeness of itself. Decades of studies have provided overwhelming evidence to support this hypothesis. The latest advances in generating infectious prions with bacterially expressed recombinant prion protein in the presence of cofactors not only provide convincing evidence supporting the ‘protein-only hypothesis’, but also indicate a role of cofactors in forming prion infectivity and encoding prion strains. In the present chapter, we review the literature regarding the chemical nature of the infectious agent, describe recent achievements in proving the ‘protein-only hypothesis’, and discuss the remaining questions in this research area.
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August 2014
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Review Article|
August 18 2014
Prion disease and the ‘protein-only hypothesis’
Jiyan Ma
;
Jiyan Ma
1
Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI 49503, U.S.A.
1Correspondence may be addressed to either of these authors (email jiyan.ma@vai.org or fei.wang@vai.org).
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Fei Wang
Fei Wang
1
Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI 49503, U.S.A.
1Correspondence may be addressed to either of these authors (email jiyan.ma@vai.org or fei.wang@vai.org).
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Essays Biochem (2014) 56: 181–191.
Citation
Sarah Perrett, Jiyan Ma, Fei Wang; Prion disease and the ‘protein-only hypothesis’. Essays Biochem 18 August 2014; 56 181–191. doi: https://doi.org/10.1042/bse0560181
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