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Frataxin deficiency is associated with imbalances in iron-sulfur containing proteins, mitochondrial respiratory chain dysfunction and lower ATP production, and accumulation of iron in the mitochondria, which increases oxidative stress and oxidative damage to macromolecules of the respiratory chain (77)

These factors frequently cause neurons to be under stress, which in turn causes cytotoxic events such as an increase in excitotoxicity, ROS, synaptic dysfunction, ER stress, impaired protein degradation systems, DNA damage, cell cycle re-entry, inflammation, and mitochondrial dysfunction (Seward et al., 2013)

High ROS levels cause lipid, protein, and DNA damage

doi: 10.3389/fphar.2026.1694895 Received 29 August 2025 Revised 30 November 2025 Accepted 12 January 2026 Published 13 February 2026 Volume 17 - 2026 Edited by Ji Yichun, University of California, San Diego, United States Reviewed by Janina P

doi: 10.5534/wjmh.230291