A Protein Misfolding Shaking Amplification-based method for the spontaneous generation of hundreds of bona fide prions.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38459071.
- Also identified by DOI 10.1038/s41467-024-46360-2 and PMC identifier 10923866.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Prion diseases are a group of rapidly progressing neurodegenerative disorders caused by the misfolding of the endogenous prion protein (PrP<sup>C</sup>) into a pathogenic form (PrP<sup>Sc</sup>). This process, despite being the central event underlying these disorders, remains largely unknown at a molecular level, precluding the prediction of new potential outbreaks or interspecies transmission incidents. In this work, we present a method to generate bona fide recombinant prions de novo, allowing a comprehensive analysis of protein misfolding across a wide range of prion proteins from mammalian species. We study more than 380 different prion proteins from mammals and classify them according to their spontaneous misfolding propensity and their conformational variability. This study aims to address fundamental questions in the prion research field such as defining infectivity determinants, interspecies transmission barriers or the structural influence of specific amino acids and provide invaluable information for future diagnosis and therapy applications.
Medical subject headings
- Prions
- Prion Diseases