A Protein Misfolding Shaking Amplificationbased method for the spontaneous generation of hundreds of bona fide prions
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Author
Eraña, Hasier
Sampedro-Torres-Quevedo, Cristina
Charco, Jorge M.
Díaz-Domínguez, Carlos M.
Peccati, Francesca
San-Juan-Ansoleaga, Maitena
Gonçalves-Anjo, Nuno
Pérez-Castro, Miguel A.
González-Miranda, Ezequiel
Piñeiro, Patricia
Fernández-Veiga, Leire
Galarza-Ahumada, Josu
Fernández-Muñoz, Eva
Perez de Nanclares, Guiomar
Telling, Glenn
Geijo, Mariví
Jiménez-Osés, Gonzalo
Castilla, Joaquín
Publication date
2024-03-08ISSN
2041-1723
Abstract
Prion diseases are a group of rapidly progressing neurodegenerative disorders
caused by the misfolding of the endogenous prion protein (PrPC) into a
pathogenic form (PrPSc). 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.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
619 - Veterinary science
Pages
14
Publisher
Nature Research
Is part of
Nature Communications
Citation
Eraña, Hasier, Cristina Sampedro-Torres-Quevedo, Jorge M. Charco, Carlos M. Díaz-Domínguez, Francesca Peccati, Maitena San-Juan-Ansoleaga, Enríc Vidal, et al. 2024. “A Protein Misfolding Shaking Amplification-based Method for the Spontaneous Generation of Hundreds of Bona Fide Prions.” Nature Communications 15: 2112. doi:10.1038/s41467-024-46360-2.
Grant agreement number
MICINN/Programa Estatal para impulsar la investigación científico-técnica y su transferencia/PID2021-122201OB-C21/ES/ANALISIS DEL MALPLEGAMIENTO IN VITRO DE UNA DIVERSIDAD DE PROTEINAS DEL PRION PARA LA GENERACION DE NUEVAS ENTIDADES INFECCIOSAS Y DESARROLLO DE APROXIMACIONES TERAPEUTICAS/
MICINN/Programa Estatal para impulsar la investigación científico-técnica y su transferencia/PID2021-122201OB-C22/ES/DESARROLLO DE INNOVADORES MODELOS DE ENFERMEDADES PRIONICAS Y ESTUDIO DE LA PATOBIOLOGIA DE PRIONES SINTETICOS EN RATONES TRANSGENICOS Y HOSPEDADORES POCO COMUNES/
MICINN/Programa Estatal para impulsar la investigación científico-técnica y su transferencia/PID2021-125946OB-I00/ES/ INGENIERIA DE GANANCIA DE FUNCION DE PROTEINAS IN SILICO PARA NUEVAS APLICACIONES Y TERAPIAS/
MICINN/Programa Estatal de promoción del talento y su empleabilidad en I+D+I/IJC2020-045506-I/ES/ /
FEDER/ / /EU/ /
ISCIII/ /AC21_2-00024/ES/Biomarcadores prodrómicos en Insomnio Familiar Letal: Un estudio longitudinal en humanos y ratones/
MICINN/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I/CEX2021-001136-S/ES/ /
Program
Sanitat Animal
This item appears in the following Collection(s)
- ARTICLES CIENTÍFICS [2685]
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/