Cofactors facilitate bona fide prion misfolding in vitro but are not necessary for the infectivity of recombinant murine prions.
Prion diseases, particularly sporadic cases, pose a challenge due to their complex nature and heterogeneity. The underlying mechanism of the spontaneous conversion from PrPC to PrPSc, the hallmark of prion diseases, remains elusive. To shed light on this process and the involvement of cofactors, we...
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| Format: | Article |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012890 |
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| author | Miguel Ángel Pérez-Castro Hasier Eraña Enric Vidal Jorge M Charco Nuria L Lorenzo Nuno Gonçalves-Anjo Josu Galarza-Ahumada Carlos M Díaz-Domínguez Patricia Piñeiro Ezequiel González-Miranda Samanta Giler Glenn Telling Manuel A Sánchez-Martín Joseba Garrido Mariví Geijo Jesús R Requena Joaquín Castilla |
| author_facet | Miguel Ángel Pérez-Castro Hasier Eraña Enric Vidal Jorge M Charco Nuria L Lorenzo Nuno Gonçalves-Anjo Josu Galarza-Ahumada Carlos M Díaz-Domínguez Patricia Piñeiro Ezequiel González-Miranda Samanta Giler Glenn Telling Manuel A Sánchez-Martín Joseba Garrido Mariví Geijo Jesús R Requena Joaquín Castilla |
| author_sort | Miguel Ángel Pérez-Castro |
| collection | DOAJ |
| description | Prion diseases, particularly sporadic cases, pose a challenge due to their complex nature and heterogeneity. The underlying mechanism of the spontaneous conversion from PrPC to PrPSc, the hallmark of prion diseases, remains elusive. To shed light on this process and the involvement of cofactors, we have developed an in vitro system that faithfully mimics spontaneous prion misfolding using minimal components. By employing this PMSA methodology and introducing an isoleucine residue at position 108 in mouse PrP, we successfully generated recombinant murine prion strains with distinct biochemical and biological properties. Our study aimed to explore the influence of a polyanionic cofactor in modulating strain selection and infectivity in de novo-generated synthetic prions. These results not only validate PMSA as a robust method for generating diverse bona fide recombinant prions but also emphasize the significance of cofactors in shaping specific prion conformers capable of crossing species barriers. Interestingly, once these conformers are established, our findings suggest that cofactors are not necessary for their infectivity. This research provides valuable insights into the propagation and maintenance of the pathobiological features of cross-species transmissible recombinant murine prion and highlights the intricate interplay between cofactors and prion strain characteristics. |
| format | Article |
| id | doaj-art-7ecfd6dccd0d41e08f6cfbe9930c714e |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-7ecfd6dccd0d41e08f6cfbe9930c714e2025-02-05T05:30:53ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-01-01211e101289010.1371/journal.ppat.1012890Cofactors facilitate bona fide prion misfolding in vitro but are not necessary for the infectivity of recombinant murine prions.Miguel Ángel Pérez-CastroHasier ErañaEnric VidalJorge M CharcoNuria L LorenzoNuno Gonçalves-AnjoJosu Galarza-AhumadaCarlos M Díaz-DomínguezPatricia PiñeiroEzequiel González-MirandaSamanta GilerGlenn TellingManuel A Sánchez-MartínJoseba GarridoMariví GeijoJesús R RequenaJoaquín CastillaPrion diseases, particularly sporadic cases, pose a challenge due to their complex nature and heterogeneity. The underlying mechanism of the spontaneous conversion from PrPC to PrPSc, the hallmark of prion diseases, remains elusive. To shed light on this process and the involvement of cofactors, we have developed an in vitro system that faithfully mimics spontaneous prion misfolding using minimal components. By employing this PMSA methodology and introducing an isoleucine residue at position 108 in mouse PrP, we successfully generated recombinant murine prion strains with distinct biochemical and biological properties. Our study aimed to explore the influence of a polyanionic cofactor in modulating strain selection and infectivity in de novo-generated synthetic prions. These results not only validate PMSA as a robust method for generating diverse bona fide recombinant prions but also emphasize the significance of cofactors in shaping specific prion conformers capable of crossing species barriers. Interestingly, once these conformers are established, our findings suggest that cofactors are not necessary for their infectivity. This research provides valuable insights into the propagation and maintenance of the pathobiological features of cross-species transmissible recombinant murine prion and highlights the intricate interplay between cofactors and prion strain characteristics.https://doi.org/10.1371/journal.ppat.1012890 |
| spellingShingle | Miguel Ángel Pérez-Castro Hasier Eraña Enric Vidal Jorge M Charco Nuria L Lorenzo Nuno Gonçalves-Anjo Josu Galarza-Ahumada Carlos M Díaz-Domínguez Patricia Piñeiro Ezequiel González-Miranda Samanta Giler Glenn Telling Manuel A Sánchez-Martín Joseba Garrido Mariví Geijo Jesús R Requena Joaquín Castilla Cofactors facilitate bona fide prion misfolding in vitro but are not necessary for the infectivity of recombinant murine prions. PLoS Pathogens |
| title | Cofactors facilitate bona fide prion misfolding in vitro but are not necessary for the infectivity of recombinant murine prions. |
| title_full | Cofactors facilitate bona fide prion misfolding in vitro but are not necessary for the infectivity of recombinant murine prions. |
| title_fullStr | Cofactors facilitate bona fide prion misfolding in vitro but are not necessary for the infectivity of recombinant murine prions. |
| title_full_unstemmed | Cofactors facilitate bona fide prion misfolding in vitro but are not necessary for the infectivity of recombinant murine prions. |
| title_short | Cofactors facilitate bona fide prion misfolding in vitro but are not necessary for the infectivity of recombinant murine prions. |
| title_sort | cofactors facilitate bona fide prion misfolding in vitro but are not necessary for the infectivity of recombinant murine prions |
| url | https://doi.org/10.1371/journal.ppat.1012890 |
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