Skip to main content

ORIGINAL RESEARCH article

Front. Mol. Neurosci.

Sec. Molecular Signalling and Pathways

Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1571402

Redox homeostasis and Inflammation in fibroblasts of patients with Friedreich Ataxia: a possible cross talk

Provisionally accepted
  • 1 Unit of Muscular and Neurodegenerative Diseases, Rome, Italy
  • 2 Bambino Gesù Children's Hospital (IRCCS), Rome, Italy
  • 3 Research Unit of Neuromuscular Diseases, Rome, Italy

The final, formatted version of the article will be published soon.

    Redox homeostasis is impaired in Friedreich's Ataxia (FRDA), a neurodegenerative disease caused by the decreased expression of the mitochondrial protein frataxin. Nrf2, the master regulator of tissue redox balance, is defective in the disease, driving cells to ferroptosis. Neuro-inflammation is recently emerging as an additional pathological mechanism in FRDA and has to be understood in order to go deeper into the pathogenesis of the disease. As a functional cross talk between Nrf2 and NF-kB pathways has been previously reported, we wonder if inflammation may be activated in FRDA as a consequence of Nrf2 deficiency. Thus, we analyzed the expression of proteins involved in the antioxidant and inflammatory responses in fibroblasts of patients with FRDA. We found a significant activation of the TLR4/NF-kB/IL-1β axis in patients, associated to a consistent increase of the redox enzymes thioredoxin 1 (TRX1) and glutaredoxin 1 (GLRX1), which are essential to activate NF-kB under oxidative stress conditions. Furthermore, we investigated the role of 4-HNE, a by-product of lipid peroxidation, as a potential mediator between ferroptosis and inflammation in FRDA.

    Keywords: Freidreich Ataxia, Nrf2, NF-kB, TLR4, GLRX1, Trx1, IL-1β

    Received: 05 Feb 2025; Accepted: 25 Mar 2025.

    Copyright: © 2025 Quatrana, Petrillo, Torda, De Santis, Bertini and Piemonte. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Fiorella Piemonte, Bambino Gesù Children's Hospital (IRCCS), Rome, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

    Research integrity at Frontiers

    Man ultramarathon runner in the mountains he trains at sunset

    95% of researchers rate our articles as excellent or good

    Learn more about the work of our research integrity team to safeguard the quality of each article we publish.


    Find out more