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This deficit has been linked to a cascade of biochemical alterations, including mitochondrial dysfunction, oxidative stress and neuronal apoptosis, that drives the neurodegenerative process. FRDA is a very incapacitating disease and patients rely on very limited therapeutic alternatives, such as the recently approved drug omaveloxolone, to treat the oxidative stress. Nevertheless, previous studies have suggested the activation of the brain-derived neurotrophic factor (BDNF) may be a promising treatment to regulate FRDA pathophysiology. Herein, we characterize the effects of FXN deficiency in an in vitro model of primary cerebellar granule neurons (CGNs) derived from the FRDA mouse model YG8-800, as well as the therapeutic potential of BDNF partial agonism by the small molecule 7,8-dihydroxyflavone (7,8-DHF). We found evidence of mitochondrial dysfunction concomitant with DNA damage and enhanced cell death due to FXN deficiency in cultured neurons. The treatment with 7,8-DHF was able to reduce the markers of genotoxicity and apoptosis, without restoring the impaired mitochondrial function nor the total cell death, possibly through ferroptosis, revealing a partial neuroprotective effect insufficient to halt the neurodegenerative process in this in vitro model of FRDA.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s12035-026-05856-2","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T06:55:23Z","timestamp":1776840923000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The TRKB Agonist 7,8-dihydroxyflavone Alleviates DNA Damage and Apoptosis in a Neuronal Cell Model of Friedreich\u2019s Ataxia"],"prefix":"10.1007","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7596-2111","authenticated-orcid":false,"given":"Jorge","family":"Gal\u00e1n-Cruz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5106-5264","authenticated-orcid":false,"given":"Andr\u00e9s","family":"Vicente-Acosta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5655-4331","authenticated-orcid":false,"given":"Frida","family":"Lor\u00eda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0927-7925","authenticated-orcid":false,"given":"Javier","family":"D\u00edaz-Nido","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9239-2704","authenticated-orcid":false,"given":"Sa\u00fal","family":"Herranz-Mart\u00edn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"5856_CR1","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1126\/science.271.5254.1423","volume":"271","author":"V Campuzano","year":"1996","unstructured":"Campuzano V, Montermini L, Molt\u00f2 MD et al (1996) Friedreich\u2019s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. 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