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The controversial protein-only hypothesis of prion propagation

Abstract

Prion diseases are some of the most intriguing infectious disorders affecting the brains of humans and animals. The prevalent hypothesis proposes that the infectious agent is a misfolded protein that propagates in the absence of nucleic acid by transmission of its altered folding to the normal host version of the protein. This article details the evidence for and against the prion hypothesis, including results of recent studies in yeast, in which a prion phenomenon has also been identified. The evidence in favor of the prion model is very strong, but final proof—consisting of the generation of infectious prions in vitro—is still missing.

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Figure 1
Figure 2
Figure 3: In vitro formation of amyloid fibrils by recombinant fragment of yeast Sup35 labeled with GFP seeded by Sup35 aggregates.

Chi-yen King; reprinted from Nature

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Acknowledgements

We thanks K. Maundrell (Serono), K. Abid and P. Saa (University of Texas Medical Branch) for critical reading of the manuscript and for helpful discussions.

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Correspondence to Claudio Soto.

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Soto, C., Castilla, J. The controversial protein-only hypothesis of prion propagation. Nat Med 10, S63–S67 (2004). https://doi.org/10.1038/nm1069

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