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Early Access

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

Publicated to:PROGRESS IN NEUROBIOLOGY. 102743-102743 - 2025-02-26 (), DOI: 10.1016/j.pneurobio.2025.102743

Authors: Antón-Fernández A; de Alegría ÁR; Mariscal-Casero A; Roldán-Lázaro M; Peinado-Cauchola R; Ávila J; Hernández F

Affiliations

Centro de Biología Molecular Severo Ochoa (UAM-CSIC). Nicolás Cabrera, 1. Cantoblanco. 28049 Madrid, Spain. - Author
Centro de Biología Molecular Severo Ochoa (UAM-CSIC). Nicolás Cabrera, 1. Cantoblanco. 28049 Madrid, Spain. Electronic address: aanton@cbm.csic.es. - Author
Centro de Biología Molecular Severo Ochoa (UAM-CSIC). Nicolás Cabrera, 1. Cantoblanco. 28049 Madrid, Spain. Electronic address: fhernandez@cbm.csic.es. - Author
Centro de Biología Molecular Severo Ochoa (UAM-CSIC). Nicolás Cabrera, 1. Cantoblanco. 28049 Madrid, Spain; Consejo Superior de Investigaciones Científicas (CSIC). Serrano 117. 28006 Madrid, Spain. - Author

Abstract

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.

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Quality index

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-18:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 1.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 1 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 10.5.
  • The number of mentions in news outlets: 1 (Altmetric).

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: Last Author (HERNANDEZ PEREZ, FELIX).