Partial reprogramming by cyclical overexpression of Yamanaka factors improves pathological phenotypes of tauopathy mouse model of human Alzheimer's disease

Partial reprogramming induced by the controlled and cyclical overexpression of Yamanaka factors in the nervous system has so far succeeded in reversing some aging-associated phenotypes, such as improving memory function. These promising results suggest that partial reprogramming could be a potential...

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Autores: Antón-Fernández, Alejandro, Ruiz de Alegría, Álvaro, Mariscal-Casero, Ana, Roldán-Lázaro, Marta, Peinado-Cauchola, Rocío, Ávila, Jesús, Hernández, Félix
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/398544
Acceso en línea:http://hdl.handle.net/10261/398544
Access Level:acceso abierto
Palabra clave:Alzheimer
Tau-P301S
in vivo partial reprogramming
Transgenic mice
Yamanaka factors
Tau
H3K9me3
GFAP
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spelling Partial reprogramming by cyclical overexpression of Yamanaka factors improves pathological phenotypes of tauopathy mouse model of human Alzheimer's diseaseAntón-Fernández, AlejandroRuiz de Alegría, ÁlvaroMariscal-Casero, AnaRoldán-Lázaro, MartaPeinado-Cauchola, RocíoÁvila, JesúsHernández, FélixAlzheimerTau-P301Sin vivo partial reprogrammingTransgenic miceYamanaka factorsTauH3K9me3GFAPPartial reprogramming induced by the controlled and cyclical overexpression of Yamanaka factors in the nervous system has so far succeeded in reversing some aging-associated phenotypes, such as improving memory function. These promising results suggest that partial reprogramming could be a potential strategy to prevent or mitigate aging-related pathologies like tauopathies, including Alzheimer’s disease. Here, we explore the potential of this strategy in addressing tauopathy development in the P301S mouse model. To achieve this, a new transgenic animal was created that can inducibly overexpress Yamanaka factors upon doxycycline administration and carries the Tau-P301S mutation, which leads to tauopathy development. The results of this study show a significant improvement in key pathological features of tauopathies in the hippocampus, including reversed tauopathy, alleviated reactive astrogliosis, age-related reduction of the H3K9me3 epigenetic marker, along with improved spatial memory, which has been described as deteriorated in this model. These findings reinforce the potential of partial reprogramming as a therapeutic strategy to combat brain pathologies associated with aging.Work in the laboratory of FH is funded by grants from the Spanish Ministry of Economy and Competitiveness (Ministerio de Economía, Industria y Competitividad, Gobierno de España, PID2020–113204GB-I00) and Fundación Ramón Areces. Work in the laboratory of JA is funded by grants from the Spanish Ministry of Economy and Competitiveness (PGC-2018–09177-B-100). The Centro de Biología Molecular Severo Ochoa (CBMSO) is a Severo Ochoa Center of Excellence (MICIN, award CEX2021–001154-S).Peer reviewedMinisterio de Economía, Industria y Competitividad (España)Fundación Ramón ArecesMinisterio de Economía y Competitividad (España)CSIC-UAM - Centro de Biología Molecular Severo Ochoa (CBM)Agencia Estatal de Investigación (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/398544reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113204GB-I00Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3985442026-05-22T06:33:51Z
dc.title.none.fl_str_mv Partial reprogramming by cyclical overexpression of Yamanaka factors improves pathological phenotypes of tauopathy mouse model of human Alzheimer's disease
title Partial reprogramming by cyclical overexpression of Yamanaka factors improves pathological phenotypes of tauopathy mouse model of human Alzheimer's disease
spellingShingle Partial reprogramming by cyclical overexpression of Yamanaka factors improves pathological phenotypes of tauopathy mouse model of human Alzheimer's disease
Antón-Fernández, Alejandro
Alzheimer
Tau-P301S
in vivo partial reprogramming
Transgenic mice
Yamanaka factors
Tau
H3K9me3
GFAP
title_short Partial reprogramming by cyclical overexpression of Yamanaka factors improves pathological phenotypes of tauopathy mouse model of human Alzheimer's disease
title_full Partial reprogramming by cyclical overexpression of Yamanaka factors improves pathological phenotypes of tauopathy mouse model of human Alzheimer's disease
title_fullStr Partial reprogramming by cyclical overexpression of Yamanaka factors improves pathological phenotypes of tauopathy mouse model of human Alzheimer's disease
title_full_unstemmed Partial reprogramming by cyclical overexpression of Yamanaka factors improves pathological phenotypes of tauopathy mouse model of human Alzheimer's disease
title_sort Partial reprogramming by cyclical overexpression of Yamanaka factors improves pathological phenotypes of tauopathy mouse model of human Alzheimer's disease
dc.creator.none.fl_str_mv Antón-Fernández, Alejandro
Ruiz de Alegría, Álvaro
Mariscal-Casero, Ana
Roldán-Lázaro, Marta
Peinado-Cauchola, Rocío
Ávila, Jesús
Hernández, Félix
author Antón-Fernández, Alejandro
author_facet Antón-Fernández, Alejandro
Ruiz de Alegría, Álvaro
Mariscal-Casero, Ana
Roldán-Lázaro, Marta
Peinado-Cauchola, Rocío
Ávila, Jesús
Hernández, Félix
author_role author
author2 Ruiz de Alegría, Álvaro
Mariscal-Casero, Ana
Roldán-Lázaro, Marta
Peinado-Cauchola, Rocío
Ávila, Jesús
Hernández, Félix
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía, Industria y Competitividad (España)
Fundación Ramón Areces
Ministerio de Economía y Competitividad (España)
CSIC-UAM - Centro de Biología Molecular Severo Ochoa (CBM)
Agencia Estatal de Investigación (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Alzheimer
Tau-P301S
in vivo partial reprogramming
Transgenic mice
Yamanaka factors
Tau
H3K9me3
GFAP
topic Alzheimer
Tau-P301S
in vivo partial reprogramming
Transgenic mice
Yamanaka factors
Tau
H3K9me3
GFAP
description Partial reprogramming induced by the controlled and cyclical overexpression of Yamanaka factors in the nervous system has so far succeeded in reversing some aging-associated phenotypes, such as improving memory function. These promising results suggest that partial reprogramming could be a potential strategy to prevent or mitigate aging-related pathologies like tauopathies, including Alzheimer’s disease. Here, we explore the potential of this strategy in addressing tauopathy development in the P301S mouse model. To achieve this, a new transgenic animal was created that can inducibly overexpress Yamanaka factors upon doxycycline administration and carries the Tau-P301S mutation, which leads to tauopathy development. The results of this study show a significant improvement in key pathological features of tauopathies in the hippocampus, including reversed tauopathy, alleviated reactive astrogliosis, age-related reduction of the H3K9me3 epigenetic marker, along with improved spatial memory, which has been described as deteriorated in this model. These findings reinforce the potential of partial reprogramming as a therapeutic strategy to combat brain pathologies associated with aging.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/398544
url http://hdl.handle.net/10261/398544
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113204GB-I00
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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