Understanding the key features of the spontaneous formation of bona fide prions through a novel methodology that enables their swift and consistent generation

Among transmissible spongiform encephalopathies or prion diseases affecting humans, sporadic forms such as sporadic Creutzfeldt-Jakob disease are the vast majority. Unlike genetic or acquired forms of the disease, these idiopathic forms occur seemingly due to a random event of spontaneous misfolding...

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Autores: Eraña, Hasier|||0000-0001-8776-4211, Díaz-Domínguez, Carlos M.|||0000-0002-0410-1963, Charco, Jorge M.|||0000-0003-3476-1855, Vidal Barba, Enric|||0000-0002-4965-3286, González-Miranda, Ezequiel, Pérez-Castro, Miguel A.|||0000-0003-2850-3470, Piñeiro, Patricia|||0000-0002-0062-2542, López-Moreno, Rafael, Sampedro-Torres-Quevedo, Cristina|||0000-0001-6374-1760, Fernández-Veiga, Leire, Tasis-Galarza, Juan, Lorenzo, Nuria L., Santini-Santiago, Aileen, Lázaro, Melisa, García-Martínez, Sandra|||0000-0002-6910-9202, Gonçalves-Anjo, Nuno|||0000-0003-0586-2550, San-Juan-Ansoleaga, Maitena|||0000-0001-7968-510X, Galarza-Ahumada, Josu|||0000-0003-0275-559X, Fernández-Muñoz, Eva, Giler, Samanta, Valle, Mikel, Telling, Glenn C., Geijó, Mariví, Requena, Jesús R., Castilla, Joaquín|||0000-0002-2216-1361
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:320153
Acesso em linha:https://ddd.uab.cat/record/320153
https://dx.doi.org/urn:doi:10.1186/s40478-023-01640-8
Access Level:acceso abierto
Palavra-chave:Prion
Transmissible spongiform encephalopathies
Spontaneous misfolding
Strain
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spelling Understanding the key features of the spontaneous formation of bona fide prions through a novel methodology that enables their swift and consistent generationEraña, Hasier|||0000-0001-8776-4211Díaz-Domínguez, Carlos M.|||0000-0002-0410-1963Charco, Jorge M.|||0000-0003-3476-1855Vidal Barba, Enric|||0000-0002-4965-3286González-Miranda, EzequielPérez-Castro, Miguel A.|||0000-0003-2850-3470Piñeiro, Patricia|||0000-0002-0062-2542López-Moreno, RafaelSampedro-Torres-Quevedo, Cristina|||0000-0001-6374-1760Fernández-Veiga, LeireTasis-Galarza, JuanLorenzo, Nuria L.Santini-Santiago, AileenLázaro, MelisaGarcía-Martínez, Sandra|||0000-0002-6910-9202Gonçalves-Anjo, Nuno|||0000-0003-0586-2550San-Juan-Ansoleaga, Maitena|||0000-0001-7968-510XGalarza-Ahumada, Josu|||0000-0003-0275-559XFernández-Muñoz, EvaGiler, SamantaValle, MikelTelling, Glenn C.Geijó, MarivíRequena, Jesús R.Castilla, Joaquín|||0000-0002-2216-1361PrionTransmissible spongiform encephalopathiesSpontaneous misfoldingStrainAmong transmissible spongiform encephalopathies or prion diseases affecting humans, sporadic forms such as sporadic Creutzfeldt-Jakob disease are the vast majority. Unlike genetic or acquired forms of the disease, these idiopathic forms occur seemingly due to a random event of spontaneous misfolding of the cellular PrP (PrPC) into the pathogenic isoform (PrPSc). Currently, the molecular mechanisms that trigger and drive this event, which occurs in approximately one individual per million each year, remain completely unknown. Modelling this phenomenon in experimental settings is highly challenging due to its sporadic and rare occurrence. Previous attempts to model spontaneous prion misfolding in vitro have not been fully successful, as the spontaneous formation of prions is infrequent and stochastic, hindering the systematic study of the phenomenon. In this study, we present the first method that consistently induces spontaneous misfolding of recombinant PrP into bona fide prions within hours, providing unprecedented possibilities to investigate the mechanisms underlying sporadic prionopathies. By fine-tuning the Protein Misfolding Shaking Amplification method, which was initially developed to propagate recombinant prions, we have created a methodology that consistently produces spontaneously misfolded recombinant prions in 100% of the cases. Furthermore, this method gives rise to distinct strains and reveals the critical influence of charged surfaces in this process. 22023-01-0120232023-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/320153https://dx.doi.org/urn:doi:10.1186/s40478-023-01640-8reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2021-122201OB-C21Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2021-1222010B-C22Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2020-117465GB-I00Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 AC21_2/00024open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3201532026-06-06T12:50:31Z
dc.title.none.fl_str_mv Understanding the key features of the spontaneous formation of bona fide prions through a novel methodology that enables their swift and consistent generation
title Understanding the key features of the spontaneous formation of bona fide prions through a novel methodology that enables their swift and consistent generation
spellingShingle Understanding the key features of the spontaneous formation of bona fide prions through a novel methodology that enables their swift and consistent generation
Eraña, Hasier|||0000-0001-8776-4211
Prion
Transmissible spongiform encephalopathies
Spontaneous misfolding
Strain
title_short Understanding the key features of the spontaneous formation of bona fide prions through a novel methodology that enables their swift and consistent generation
title_full Understanding the key features of the spontaneous formation of bona fide prions through a novel methodology that enables their swift and consistent generation
title_fullStr Understanding the key features of the spontaneous formation of bona fide prions through a novel methodology that enables their swift and consistent generation
title_full_unstemmed Understanding the key features of the spontaneous formation of bona fide prions through a novel methodology that enables their swift and consistent generation
title_sort Understanding the key features of the spontaneous formation of bona fide prions through a novel methodology that enables their swift and consistent generation
dc.creator.none.fl_str_mv Eraña, Hasier|||0000-0001-8776-4211
Díaz-Domínguez, Carlos M.|||0000-0002-0410-1963
Charco, Jorge M.|||0000-0003-3476-1855
Vidal Barba, Enric|||0000-0002-4965-3286
González-Miranda, Ezequiel
Pérez-Castro, Miguel A.|||0000-0003-2850-3470
Piñeiro, Patricia|||0000-0002-0062-2542
López-Moreno, Rafael
Sampedro-Torres-Quevedo, Cristina|||0000-0001-6374-1760
Fernández-Veiga, Leire
Tasis-Galarza, Juan
Lorenzo, Nuria L.
Santini-Santiago, Aileen
Lázaro, Melisa
García-Martínez, Sandra|||0000-0002-6910-9202
Gonçalves-Anjo, Nuno|||0000-0003-0586-2550
San-Juan-Ansoleaga, Maitena|||0000-0001-7968-510X
Galarza-Ahumada, Josu|||0000-0003-0275-559X
Fernández-Muñoz, Eva
Giler, Samanta
Valle, Mikel
Telling, Glenn C.
Geijó, Mariví
Requena, Jesús R.
Castilla, Joaquín|||0000-0002-2216-1361
author Eraña, Hasier|||0000-0001-8776-4211
author_facet Eraña, Hasier|||0000-0001-8776-4211
Díaz-Domínguez, Carlos M.|||0000-0002-0410-1963
Charco, Jorge M.|||0000-0003-3476-1855
Vidal Barba, Enric|||0000-0002-4965-3286
González-Miranda, Ezequiel
Pérez-Castro, Miguel A.|||0000-0003-2850-3470
Piñeiro, Patricia|||0000-0002-0062-2542
López-Moreno, Rafael
Sampedro-Torres-Quevedo, Cristina|||0000-0001-6374-1760
Fernández-Veiga, Leire
Tasis-Galarza, Juan
Lorenzo, Nuria L.
Santini-Santiago, Aileen
Lázaro, Melisa
García-Martínez, Sandra|||0000-0002-6910-9202
Gonçalves-Anjo, Nuno|||0000-0003-0586-2550
San-Juan-Ansoleaga, Maitena|||0000-0001-7968-510X
Galarza-Ahumada, Josu|||0000-0003-0275-559X
Fernández-Muñoz, Eva
Giler, Samanta
Valle, Mikel
Telling, Glenn C.
Geijó, Mariví
Requena, Jesús R.
Castilla, Joaquín|||0000-0002-2216-1361
author_role author
author2 Díaz-Domínguez, Carlos M.|||0000-0002-0410-1963
Charco, Jorge M.|||0000-0003-3476-1855
Vidal Barba, Enric|||0000-0002-4965-3286
González-Miranda, Ezequiel
Pérez-Castro, Miguel A.|||0000-0003-2850-3470
Piñeiro, Patricia|||0000-0002-0062-2542
López-Moreno, Rafael
Sampedro-Torres-Quevedo, Cristina|||0000-0001-6374-1760
Fernández-Veiga, Leire
Tasis-Galarza, Juan
Lorenzo, Nuria L.
Santini-Santiago, Aileen
Lázaro, Melisa
García-Martínez, Sandra|||0000-0002-6910-9202
Gonçalves-Anjo, Nuno|||0000-0003-0586-2550
San-Juan-Ansoleaga, Maitena|||0000-0001-7968-510X
Galarza-Ahumada, Josu|||0000-0003-0275-559X
Fernández-Muñoz, Eva
Giler, Samanta
Valle, Mikel
Telling, Glenn C.
Geijó, Mariví
Requena, Jesús R.
Castilla, Joaquín|||0000-0002-2216-1361
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Prion
Transmissible spongiform encephalopathies
Spontaneous misfolding
Strain
topic Prion
Transmissible spongiform encephalopathies
Spontaneous misfolding
Strain
description Among transmissible spongiform encephalopathies or prion diseases affecting humans, sporadic forms such as sporadic Creutzfeldt-Jakob disease are the vast majority. Unlike genetic or acquired forms of the disease, these idiopathic forms occur seemingly due to a random event of spontaneous misfolding of the cellular PrP (PrPC) into the pathogenic isoform (PrPSc). Currently, the molecular mechanisms that trigger and drive this event, which occurs in approximately one individual per million each year, remain completely unknown. Modelling this phenomenon in experimental settings is highly challenging due to its sporadic and rare occurrence. Previous attempts to model spontaneous prion misfolding in vitro have not been fully successful, as the spontaneous formation of prions is infrequent and stochastic, hindering the systematic study of the phenomenon. In this study, we present the first method that consistently induces spontaneous misfolding of recombinant PrP into bona fide prions within hours, providing unprecedented possibilities to investigate the mechanisms underlying sporadic prionopathies. By fine-tuning the Protein Misfolding Shaking Amplification method, which was initially developed to propagate recombinant prions, we have created a methodology that consistently produces spontaneously misfolded recombinant prions in 100% of the cases. Furthermore, this method gives rise to distinct strains and reveals the critical influence of charged surfaces in this process.
publishDate 2023
dc.date.none.fl_str_mv 2
2023-01-01
2023
2023-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/320153
https://dx.doi.org/urn:doi:10.1186/s40478-023-01640-8
url https://ddd.uab.cat/record/320153
https://dx.doi.org/urn:doi:10.1186/s40478-023-01640-8
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2021-122201OB-C21
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2021-1222010B-C22
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2020-117465GB-I00
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 AC21_2/00024
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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