{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:53:19Z","timestamp":1790837599770,"version":"4.1.0"},"reference-count":75,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T00:00:00Z","timestamp":1571616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>NRF2 (Nuclear factor Erythroid 2-related Factor 2) signaling is impaired in Friedreich\u2019s Ataxia (FRDA), an autosomal recessive disease characterized by progressive nervous system damage and degeneration of nerve fibers in the spinal cord and peripheral nerves. The loss of frataxin in patients results in iron sulfur cluster deficiency and iron accumulation in the mitochondria, making FRDA a fatal and debilitating condition. There are no currently approved therapies for the treatment of FRDA and molecules able to activate NRF2 have the potential to induce clinical benefits in patients. In this study, we compared the efficacy of six redox-active drugs, some already adopted in clinical trials, targeting NRF2 activation and frataxin expression in fibroblasts obtained from skin biopsies of FRDA patients. All of these drugs consistently increased NRF2 expression, but differential profiles of NRF2 downstream genes were activated. The Sulforaphane and N-acetylcysteine were particularly effective on genes involved in preventing inflammation and maintaining glutathione homeostasis, the dimethyl fumarate, omaxevolone, and EPI-743 in counteracting toxic products accumulation, the idebenone in mitochondrial protection. This study may contribute to develop synergic therapies, based on a combination of treatment molecules.<\/jats:p>","DOI":"10.3390\/ijms20205211","type":"journal-article","created":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T11:37:55Z","timestamp":1571657875000},"page":"5211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Targeting NRF2 for the Treatment of Friedreich\u2019s Ataxia: A Comparison among Drugs"],"prefix":"10.3390","volume":"20","author":[{"given":"Sara","family":"Petrillo","sequence":"first","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Diseases, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Diseases, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piergiorgio","family":"La Rosa","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Diseases, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9276-4590","authenticated-orcid":false,"given":"Enrico Silvio","family":"Bertini","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Diseases, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1825-9347","authenticated-orcid":false,"given":"Fiorella","family":"Piemonte","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Diseases, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1111\/febs.14379","article-title":"The role of Nrf2 signaling in counteracting neurodegenerative diseases","volume":"285","author":"Kostov","year":"2018","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1124\/pr.117.014753","article-title":"Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach","volume":"70","author":"Cuadrado","year":"2018","journal-title":"Pharmacol. 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