{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:55:53Z","timestamp":1783436153463,"version":"3.54.6"},"reference-count":230,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T00:00:00Z","timestamp":1595548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["SAF2015-66625-R"],"award-info":[{"award-number":["SAF2015-66625-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008054","name":"Fundaci\u00f3n Ram\u00f3n Areces","doi-asserted-by":"publisher","award":["CIVP18A3899"],"award-info":[{"award-number":["CIVP18A3899"]}],"id":[{"id":"10.13039\/100008054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003359","name":"Generalitat Valenciana","doi-asserted-by":"publisher","award":["PROMETEO\/2018\/135"],"award-info":[{"award-number":["PROMETEO\/2018\/135"]}],"id":[{"id":"10.13039\/501100003359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011597","name":"Conselleria de Sanitat Universal i Salut P\u00fablica","doi-asserted-by":"publisher","award":["Plan GenT CDEI-04\/20-C"],"award-info":[{"award-number":["Plan GenT CDEI-04\/20-C"]}],"id":[{"id":"10.13039\/501100011597","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CENTRO DE INVESTIGACI\u00d3N BIOM\u00c9DICA EN RED ENFERMEDADES RARAS","award":["ACCI-2018-22"],"award-info":[{"award-number":["ACCI-2018-22"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG-SCHN 558\/9-1"],"award-info":[{"award-number":["DFG-SCHN 558\/9-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Friedreich\u2019s ataxia is the commonest autosomal recessive ataxia among population of European descent. Despite the huge advances performed in the last decades, a cure still remains elusive. One of the most studied hallmarks of the disease is the increased production of oxidative stress markers in patients and models. This feature has been the motivation to develop treatments that aim to counteract such boost of free radicals and to enhance the production of antioxidant defenses. In this work, we present and critically review those \u201cantioxidant\u201d drugs that went beyond the disease\u2019s models and were approved for its application in clinical trials. The evaluation of these trials highlights some crucial aspects of the FRDA research. On the one hand, the analysis contributes to elucidate whether oxidative stress plays a central role or whether it is only an epiphenomenon. On the other hand, it comments on some limitations in the current trials that complicate the analysis and interpretation of their outcome. We also include some suggestions that will be interesting to implement in future studies and clinical trials.<\/jats:p>","DOI":"10.3390\/antiox9080664","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T11:16:35Z","timestamp":1595589395000},"page":"664","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Antioxidant Therapies and Oxidative Stress in Friedreich\u2019s Ataxia: The Right Path or Just a Diversion?"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5290-2266","authenticated-orcid":false,"given":"Laura R.","family":"Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Dentistry, Universitat de Val\u00e8ncia-INCLIVA, 46010 Valencia, Spain"},{"name":"Associated Unit for Rare Diseases INCLIVA-CIPF, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Lape\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Dentistry, Universitat de Val\u00e8ncia-INCLIVA, 46010 Valencia, Spain"},{"name":"Associated Unit for Rare Diseases INCLIVA-CIPF, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Calap-Quintana","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Dentistry, Universitat de Val\u00e8ncia-INCLIVA, 46010 Valencia, Spain"},{"name":"Associated Unit for Rare Diseases INCLIVA-CIPF, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5219-2022","authenticated-orcid":false,"given":"Mar\u00eda Dolores","family":"Molt\u00f3","sequence":"additional","affiliation":[{"name":"Department of Genetics, Universitat de Val\u00e8ncia-INCLIVA, 46100 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM), 46100 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Gonzalez-Cabo","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Dentistry, Universitat de Val\u00e8ncia-INCLIVA, 46010 Valencia, Spain"},{"name":"Associated Unit for Rare Diseases INCLIVA-CIPF, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2266-728X","authenticated-orcid":false,"given":"Juan Antonio","family":"Navarro Langa","sequence":"additional","affiliation":[{"name":"Institute of Zoology, Universitaetsstrasse 31, University of Regensburg, 93040 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/jnc.12215","article-title":"Prevalence gradients of Friedreich\u2019s ataxia and R1b haplotype in Europe co-localize, suggesting a common Palaeolithic origin in the Franco-Cantabrian ice age refuge","volume":"126","author":"Vankan","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1212\/WNL.54.12.2322","article-title":"Unique origin and specific ethnic distribution of the Friedreich ataxia GAA expansion","volume":"54","author":"Labuda","year":"2000","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1126\/science.271.5254.1423","article-title":"Friedreich\u2019s Ataxia: Autosomal Recessive Disease Caused by an Intronic GAA Triplet Repeat Expansion","volume":"271","author":"Campuzano","year":"1996","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/ana.24595","article-title":"Compound heterozygous FXN mutations and clinical outcome in friedreich ataxia","volume":"79","author":"Galea","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1093\/hmg\/6.11.1771","article-title":"Frataxin is Reduced in Friedreich Ataxia Patients and is Associated with Mitochondrial Membranes","volume":"6","author":"Campuzano","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7452","DOI":"10.1073\/pnas.94.14.7452","article-title":"Evolution of the Friedreich\u2019s ataxia trinucleotide repeat expansion: Founder effect and premutations","volume":"94","author":"Schmitt","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1056\/NEJM199610173351601","article-title":"Clinical and Genetic Abnormalities in Patients with Friedreich\u2019s Ataxia","volume":"335","author":"Cossee","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_8","first-page":"554","article-title":"The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia","volume":"59","author":"Filla","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"ref_9","first-page":"1","article-title":"Drosophila melanogaster Models of Friedreich\u2019s Ataxia","volume":"2018","author":"Navarro","year":"2018","journal-title":"BioMed Res. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1093\/hmg\/ddm102","article-title":"In vivo maturation of human frataxin","volume":"16","author":"Ventura","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/ng1097-215","article-title":"Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia","volume":"17","author":"Rotig","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1017\/S0317167100025580","article-title":"Pathology of the heart in Friedreich\u2019s ataxia: Review of the literature and report of one case","volume":"3","author":"Cote","year":"1976","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9132","DOI":"10.1021\/bi1013062","article-title":"Human Frataxin Is an Allosteric Switch That Activates the Fe\u2212S Cluster Biosynthetic Complex","volume":"49","author":"Tsai","year":"2010","journal-title":"Biochemistry"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Schmucker, S., Martelli, A., Colin, F., Page, A., Wattenhofer-Donz\u00e9, M., Reutenauer, L., and Puccio, H. (2011). Mammalian Frataxin: An Essential Function for Cellular Viability through an Interaction with a Preformed ISCU\/NFS1\/ISD11 Iron-Sulfur Assembly Complex. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016199"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3566","DOI":"10.1038\/s41467-019-11470-9","article-title":"Physiologically relevant reconstitution of iron-sulfur cluster biosynthesis uncovers persulfide-processing functions of ferredoxin-2 and frataxin","volume":"10","author":"Gervason","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.abb.2006.09.010","article-title":"Frataxin knockdown causes loss of cytoplasmic iron\u2013sulfur cluster functions, redox alterations and induction of heme transcripts","volume":"457","author":"Lu","year":"2007","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"41653","DOI":"10.1074\/jbc.M110.149443","article-title":"Frataxin Depletion in Yeast Triggers Up-regulation of Iron Transport Systems before Affecting Iron-Sulfur Enzyme Activities","volume":"285","author":"Obis","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.freeradbiomed.2015.03.014","article-title":"Mitoferrin modulates iron toxicity in a Drosophila model of Friedreich\u2019s ataxia","volume":"85","author":"Navarro","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/j.cell.2019.03.045","article-title":"Hypoxia Rescues Frataxin Loss by Restoring Iron Sulfur Cluster Biogenesis","volume":"177","author":"Ast","year":"2019","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6798","DOI":"10.1021\/bi025566+","article-title":"Physical evidence that yeast frataxin is an iron storage protein","volume":"41","author":"Gakh","year":"2002","journal-title":"Biochemistry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12239","DOI":"10.1073\/pnas.220403797","article-title":"Frataxin activates mitochondrial energy conversion and oxidative phosphorylation","volume":"97","author":"Ristow","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1093\/hmg\/ddi214","article-title":"Frataxin interacts functionally with mitochondrial electron transport chain proteins","volume":"14","author":"Sanz","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25943","DOI":"10.1074\/jbc.C400107200","article-title":"Frataxin-mediated iron delivery to ferrochelatase in the final step of heme biosynthesis","volume":"279","author":"Yoon","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1126\/science.1098991","article-title":"Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity","volume":"305","author":"Bulteau","year":"2004","journal-title":"Science"},{"key":"ref_25","first-page":"124","article-title":"Mitochondrial dysfunction induced by frataxin deficiency is associated with cellular senescence and abnormal calcium metabolism","volume":"8","author":"Palau","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Moll\u00e1, B., Mu\u00f1oz-Lasso, D.C., Riveiro, F., Bolinches-Amor\u00f3s, A., Pallard\u00f3, F.V., Fernandez-Vilata, A., de la Iglesia-Vaya, M., Palau, F., and Gonzalez-Cabo, P. (2017). Reversible axonal dystrophy by calcium modulation in frataxin-deficient sensory neurons of YG8R mice. Front. Mol. Neurosci., 10.","DOI":"10.3389\/fnmol.2017.00264"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fncel.2018.00264","article-title":"Calcium Deregulation: Novel Insights to Understand Friedreich\u2019s Ataxia Pathophysiology","volume":"12","author":"Abeti","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1093\/hmg\/ddt576","article-title":"Apoptotic cell death and altered calcium homeostasis caused by frataxin depletion in dorsal root ganglia neurons can be prevented by BH4 domain of Bcl-xL protein","volume":"23","author":"Obis","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/BF01930976","article-title":"Ueber degenerative Atrophie der spinalen Hinterstr\u00e4nge","volume":"26","author":"Friedreich","year":"1863","journal-title":"Arch. Pathol. Anat. Physiol. Klin. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1093\/brain\/120.12.2131","article-title":"Friedreich\u2019s ataxia. Revision of the phenotype according to molecular genetics","volume":"120","author":"Amoiridis","year":"1997","journal-title":"Brain"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1002\/(SICI)1096-8628(19991119)87:2<168::AID-AJMG8>3.0.CO;2-2","article-title":"Clinical and genetic study of Friedreich ataxia in an Australian population","volume":"87","author":"Delatycki","year":"1999","journal-title":"Am. J. Med. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1002\/mds.26382","article-title":"Delayed-onset Friedreich\u2019s ataxia revisited","volume":"31","author":"Lecocq","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jns.2011.05.023","article-title":"Mortality in Friedreich ataxia","volume":"307","author":"Tsou","year":"2011","journal-title":"J. Neurol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0022-510X(96)00231-6","article-title":"International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology","volume":"145","author":"Trouillas","year":"1997","journal-title":"J. Neurol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1002\/mds.20651","article-title":"International cooperative ataxia rating scale (ICARS): Appropriate for studies of Friedreich\u2019s ataxia?","volume":"20","author":"Cano","year":"2005","journal-title":"Mov. Disord."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1212\/01.WNL.0000156802.15466.79","article-title":"Measuring Friedreich ataxia: Interrater reliability of a neurologic rating scale","volume":"64","author":"Subramony","year":"2005","journal-title":"Neurology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1212\/01.wnl.0000219042.60538.92","article-title":"Scale for the assessment and rating of ataxia: Development of a new clinical scale","volume":"66","author":"Baliko","year":"2006","journal-title":"Neurology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1002\/acn3.332","article-title":"Progression of Friedreich ataxia: Quantitative characterization over 5 years","volume":"3","author":"Patel","year":"2016","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1212\/NXG.0000000000000371","article-title":"Psychometric properties of the Friedreich Ataxia Rating Scale","volume":"5","author":"Rummey","year":"2019","journal-title":"Neurol. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1177\/0883073812448230","article-title":"Clinical Features of Friedreich Ataxia","volume":"27","author":"Delatycki","year":"2012","journal-title":"J. Child Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1097\/NEN.0b013e31827e5762","article-title":"Friedreich Ataxia: Neuropathology Revised","volume":"72","author":"Koeppen","year":"2013","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1136\/adc.59.3.217","article-title":"Friedreich\u2019s ataxia. A clinical review with neurophysiological and echocardiographic findings","volume":"59","author":"Ackroyd","year":"1984","journal-title":"Arch. Dis. Child."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00401-010-0675-0","article-title":"Pathology and pathogenesis of sensory neuropathy in Friedreich\u2019s ataxia","volume":"120","author":"Morral","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Koeppen, A.H., Ramirez, R.L., Becker, A.B., and Mazurkiewicz, J.E. (2016). Dorsal root ganglia in Friedreich ataxia: Satellite cell proliferation and inflammation. Acta Neuropathol. Commun., 1\u201312.","DOI":"10.1186\/s40478-016-0288-5"},{"key":"ref_45","first-page":"708","article-title":"Skeletal Muscle Involvement in Friedreich Ataxia and Potential Effects of Recombinant Human Erythropoietin Administration on Muscle Regeneration and Neovascularization","volume":"71","author":"Nachbauer","year":"2012","journal-title":"Am. Assoc. Neuropatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s00401-011-0844-9","article-title":"The cerebellar component of Friedreich\u2019s ataxia","volume":"122","author":"Koeppen","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1007\/s00415-009-5079-5","article-title":"A combined voxel-based morphometry and 1 H-MRS study in patients with Friedreich\u2019s ataxia","volume":"256","author":"Yasuda","year":"2009","journal-title":"J. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1136\/jnnp.2007.124297","article-title":"Brain structural damage in Friedreich\u2019s ataxia","volume":"79","author":"Ginestroni","year":"2008","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1159\/000287207","article-title":"Dysarthria in Friedreich\u2019s ataxia: A perceptual analysis","volume":"62","author":"Folker","year":"2010","journal-title":"Folia Phoniatr. Logop."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/j.1468-1331.2006.01363.x","article-title":"Exploring mental status in Friedreich\u2019s ataxia: A combined neuropsychological, behavioral and neuroimaging study","volume":"13","author":"Mantovan","year":"2006","journal-title":"Eur. J. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1093\/brain\/awn104","article-title":"Speech perception ability in individuals with Friedreich ataxia","volume":"131","author":"Rance","year":"2008","journal-title":"Brain"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1093\/brain\/awn269","article-title":"Visual system involvement in patients with Friedreich\u2019s ataxia","volume":"132","author":"Fortuna","year":"2009","journal-title":"Brain"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1007\/s00455-017-9804-4","article-title":"Dysphagia in Friedreich Ataxia","volume":"32","author":"Keage","year":"2017","journal-title":"Dysphagia"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1161\/CIRCULATIONAHA.111.059477","article-title":"The heart in Friedreich ataxia: Definition of cardiomyopathy, disease severity, and correlation with neurological symptoms","volume":"125","author":"Weidemann","year":"2012","journal-title":"Circulation"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Koeppen, A.H., Ramirez, R.L., Becker, A.B., Bjork, S.T., Yang, X., Feustel, P.J., and Mazurkiewicz, J.E. (2015). The Pathogenesis of Cardiomyopathy in Friedreich Ataxia. PLoS ONE.","DOI":"10.1371\/journal.pone.0116396"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1002\/mds.22864","article-title":"Analysis of the factors influencing the cardiac phenotype in Friedreich\u2019s ataxia","volume":"25","author":"Rajagopalan","year":"2010","journal-title":"Mov. Disord."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1177\/0883073812448461","article-title":"Cross-Sectional Analysis of Electrocardiograms in a Large Heterogeneous Cohort of Friedreich Ataxia Subjects","volume":"27","author":"Schadt","year":"2012","journal-title":"J. Child Neurol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s11845-011-0744-y","article-title":"Friedreich\u2019s Ataxia: A review from a cardiology perspective","volume":"180","author":"Bourke","year":"2011","journal-title":"Ir. J. Med. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1212\/WNL.38.8.1292","article-title":"Glucose metabolism alterations in Friedreich\u2019s ataxia","volume":"38","author":"Finocchiaro","year":"1988","journal-title":"Neurology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/jnc.12216","article-title":"Diabetes in Friedreich ataxia","volume":"126","author":"Cnop","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1093\/hmg\/ddp183","article-title":"Functional genomic analysis of frataxin deficiency reveals tissue-specific alterations and identifies the PPARgamma pathway as a therapeutic target in Friedreich\u2019s ataxia","volume":"18","author":"Coppola","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1093\/eurheartj\/ehq443","article-title":"Impaired myocardial perfusion reserve and fibrosis in Friedreich ataxia: A mitochondrial cardiomyopathy with metabolic syndrome","volume":"32","author":"Raman","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1097\/01.blo.0000150339.74041.0e","article-title":"Surgery for Equinovarus Deformity in Friedreich\u2019s Ataxia Improves Mobility and Independence","volume":"430","author":"Delatycki","year":"2005","journal-title":"Clin. Orthop. Relat. Res.\u00ae"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1017\/S0317167100022927","article-title":"The Cardiomyopathy of Friedreich\u2019s Ataxia Morphological Observations in 3 Cases","volume":"7","author":"Lamarche","year":"1980","journal-title":"Can. J. Neurol. Sci.\/J. Can. Sci. Neurol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/S0891-5849(97)00016-6","article-title":"Iron homeostasis, oxidative stress, and DNA damage","volume":"23","author":"Meneghini","year":"1997","journal-title":"Free Radic. Biol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"11492","DOI":"10.1073\/pnas.96.20.11492","article-title":"Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia","volume":"96","author":"Lodi","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Llorens, J.V., Soriano, S., Calap-Quintana, P., Gonzalez-Cabo, P., and Molt\u00f3, M.D. (2019). The Role of Iron in Friedreich\u2019s Ataxia: Insights From Studies in Human Tissues and Cellular and Animal Models. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00075"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1212\/WNL.55.11.1752","article-title":"Increased levels of plasma malondialdehyde in Friedreich ataxia","volume":"55","author":"Emond","year":"2000","journal-title":"Neurology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1212\/WNL.55.11.1719","article-title":"Oxidative stress in patients with Friedreich ataxia","volume":"55","author":"Schulz","year":"2000","journal-title":"Neurology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1136\/adc.86.5.376","article-title":"Antioxidant enzymes in blood of patients with Friedreich\u2019s ataxia","volume":"86","author":"Tozzi","year":"2002","journal-title":"Arch. Dis. Child."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1093\/hmg\/ddx141","article-title":"Frataxin deficiency impairs mitochondrial biogenesis in cells, mice and humans","volume":"26","author":"Jasoliya","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Paupe, V., Dassa, E.P., Goncalves, S., Auch\u00e8re, F., L\u00f6nn, M., Holmgren, A., and Rustin, P. (2009). Impaired nuclear Nrf2 translocation undermines the oxidative stress response in Friedreich ataxia. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004253"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5207","DOI":"10.1038\/s41598-020-62050-7","article-title":"Cofilin dysregulation alters actin turnover in frataxin-deficient neurons","volume":"10","author":"Pallardo","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.1093\/hmg\/ddq183","article-title":"Altered lipid metabolism in a Drosophila model of Friedreich\u2019s ataxia","volume":"19","author":"Navarro","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/jnc.12322","article-title":"Co-enzyme Q10 and idebenone use in Friedreich\u2019s ataxia","volume":"126","author":"Parkinson","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1002\/mds.25058","article-title":"A0001 in Friedreich ataxia: Biochemical characterization and effects in a clinical trial","volume":"27","author":"Lynch","year":"2012","journal-title":"Mov. Disord."},{"key":"ref_77","unstructured":"(2020, April 01). Shire Safety and Pharmacology Study of VP 20629 in Adults with Friedreich\u2019s Ataxia, Available online: https:\/\/www.clinicaltrials.gov\/ct2\/show\/study\/NCT01898884."},{"key":"ref_78","unstructured":"(2020, April 02). Efficacy of EGb761 in Patients Suffering from Friedreich Ataxia\u2014Tabular View\u2014ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/record\/NCT00824512."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Qureshi, M.Y., Patterson, M.C., Clark, V., Johnson, J.N., Moutvic, M.A., Driscoll, S.W., Kemppainen, J.L., Huston, J., Anderson, J.R., and Badley, A.D. (2020). Safety and Efficacy of (+)-Epicatechin in Subjects with Friedreich\u2019s Ataxia: A Phase II, Open-Label, Prospective Study. J. Inherit. Metab. Dis., jimd.12285.","DOI":"10.1002\/jimd.12285"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1007\/s00415-016-8244-7","article-title":"Long-term treatment with thiamine as possible medical therapy for Friedreich ataxia","volume":"263","author":"Costantini","year":"2016","journal-title":"J. Neurol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/acn3.660","article-title":"Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia","volume":"6","author":"Lynch","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_82","unstructured":"(2020, July 13). RTA 408 Capsules in Patients With Friedreich\u2019s Ataxia\u2014MOXIe\u2014Full Text View\u2014ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02255435."},{"key":"ref_83","unstructured":"(2020, July 14). Reata Announces Positive Topline Results from the MOXIe Registrational Trial of Omaveloxolone in Patients with Friedreich\u2019s Ataxia\u2014Reata Pharmaceuticals. Available online: https:\/\/www.reatapharma.com\/press-releases\/reata-announces-positive-topline-results-from-the-moxie-registrational-trial-of-omaveloxolone-in-patients-with-friedreichs-ataxia\/."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1007\/s00415-015-7719-2","article-title":"An open-label trial in Friedreich ataxia suggests clinical benefit with high-dose resveratrol, without effect on frataxin levels","volume":"262","author":"Yiu","year":"2015","journal-title":"J. Neurol."},{"key":"ref_85","unstructured":"(2020, May 13). Micronised Resveratrol as a Treatment for Friedreich Ataxia\u2014Full Text View\u2014ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT03933163."},{"key":"ref_86","unstructured":"(2020, April 16). Effect of Pioglitazone Administered to Patients With Friedreich\u2019s Ataxia: Proof of Concept\u2014Full Text View\u2014ClinicalTrials.gov, Available online: https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT00811681."},{"key":"ref_87","unstructured":"(2020, July 13). A Clinical Study to Evaluate the Effect of MIN-102 on the Progression of Friedreich\u2019s Ataxia in Male and Female Patients\u2014Full Text View\u2014ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03917225."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/s00702-004-0216-x","article-title":"L-carnitine and creatine in Friedreich\u2019s ataxia. A randomized, placebo-controlled crossover trial","volume":"112","author":"Zange","year":"2005","journal-title":"J. Neural Transm."},{"key":"ref_89","unstructured":"(2020, April 03). An Open-label Study of the Effects of Acetyl-L-Carnitine on Cardiovascular Outcomes in Friedreich\u2019s Ataxia\u2014Full Text View\u2014ClinicalTrials.gov, Available online: https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT01921868."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1002\/ana.24248","article-title":"Deferiprone in Friedreich ataxia: A 6-month randomized controlled trial","volume":"76","author":"Pandolfo","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12311-010-0212-7","article-title":"Combined therapy with idebenone and deferiprone in patients with Friedreich\u2019s ataxia","volume":"10","author":"Aracil","year":"2011","journal-title":"Cerebellum"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/ane.12141","article-title":"Triple therapy with deferiprone, idebenone and riboflavin in Friedreich\u2019s ataxia\u2014Open-label trial","volume":"129","author":"Arpa","year":"2014","journal-title":"Acta Neurol. Scand."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"233","DOI":"10.2217\/nmt-2018-0013","article-title":"Double-blind, randomized and controlled trial of EPI-743 in Friedreich\u2019s ataxia","volume":"8","author":"Zesiewicz","year":"2018","journal-title":"Neurodegener. Dis. Manag."},{"key":"ref_94","unstructured":"(2020, April 22). PTC Therapeutics Provides Corporate Update and Highlights Pipeline Progress at 2020 J.P. Morgan Healthcare Conference. Available online: https:\/\/ir.ptcbio.com\/news-releases\/news-release-details\/ptc-therapeutics-provides-corporate-update-and-highlights."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/mds.27353","article-title":"Randomized, clinical trial of RT001: Early signals of efficacy in Friedreich\u2019s ataxia","volume":"33","author":"Zesiewicz","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_96","unstructured":"(2020, July 13). A Study to Assess Efficacy, Long Term Safety and Tolerability of RT001 in Subjects with Friedreich\u2019s Ataxia\u2014Full Text View\u2014ClinicalTrials.gov, Available online: https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT04102501."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4053","DOI":"10.2174\/092986711796957257","article-title":"Targeting Mitochondrial Dysfunction and Neurodegeneration by Means of Coenzyme Q10 and its Analogues","volume":"18","author":"Orsucci","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.bbrc.2010.02.147","article-title":"Coenzyme Q\u2014Biosynthesis and functions","volume":"396","author":"Bentinger","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1096\/fj.03-0240fje","article-title":"Mitochondria-targeted antioxidants protect Friedreich Ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants","volume":"17","author":"Jauslin","year":"2003","journal-title":"FASEB J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1002\/ana.1001","article-title":"Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in patients with Friedreich\u2019s ataxia","volume":"49","author":"Lodi","year":"2001","journal-title":"Ann. Neurol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1001\/archneur.62.4.621","article-title":"Antioxidant treatment of patients with Friedreich ataxia: Four-year follow-up","volume":"62","author":"Hart","year":"2005","journal-title":"Arch. Neurol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1111\/j.1468-1331.2008.02318.x","article-title":"Coenzyme Q10 and vitamin e deficiency in Friedreich\u2019s ataxia: Predictor of efficacy of vitamin e and coenzyme Q10 therapy","volume":"15","author":"Cooper","year":"2008","journal-title":"Eur. J. Neurol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2165\/00002512-199405020-00007","article-title":"Idebenone: A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Use in Age-Related Cognitive Disorders","volume":"5","author":"Gillis","year":"1994","journal-title":"Drugs Aging"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.gene.2013.02.049","article-title":"Deferiprone and idebenone rescue frataxin depletion phenotypes in a Drosophila model of Friedreich\u2019s ataxia","volume":"521","author":"Soriano","year":"2013","journal-title":"Gene"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/hmg\/ddh114","article-title":"Idebenone delays the onset of cardiac functional alteration without correction of Fe-S enzymes deficit in a mouse model for Friedreich ataxia","volume":"13","author":"Seznec","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S0140-6736(99)01341-0","article-title":"Effect of idebenone on cardiomyopathy in Friedreich\u2019s ataxia: A preliminary study","volume":"354","author":"Rustin","year":"1999","journal-title":"Lancet"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/S1474-4422(07)70220-X","article-title":"Neurological effects of high-dose idebenone in patients with Friedreich\u2019s ataxia: A randomised, placebo-controlled trial","volume":"6","author":"Baker","year":"2007","journal-title":"Lancet Neurol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1001\/archneurol.2010.168","article-title":"A phase 3, double-blind, placebo-controlled trial of idebenone in Friedreich Ataxia","volume":"67","author":"Lynch","year":"2010","journal-title":"Arch. Neurol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.ahj.2010.10.038","article-title":"Idebenone in Friedreich ataxia cardiomyopathy-results from a 6-month phase III study (IONIA)","volume":"161","author":"Lagedrost","year":"2011","journal-title":"Am. Heart J."},{"key":"ref_110","unstructured":"(2020, March 31). A Study of Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich\u2019s Ataxia (FRDA) Patients\u2014Full Text View\u2014ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00905268."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/ane.13088","article-title":"Patient-reported outcomes in Friedreich\u2019s ataxia after withdrawal from idebenone","volume":"139","author":"Cook","year":"2019","journal-title":"Acta Neurol. Scand."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Kearney, M., Orrell, R.W., Fahey, M., and Pandolfo, M. (2009). Antioxidants and other pharmacological treatments for Friedreich ataxia. Cochrane Database Syst. Rev.","DOI":"10.1002\/14651858.CD007791.pub2"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1177\/0091270010390807","article-title":"Use of an adaptive study design in single ascending-dose pharmacokinetics of A0001 (\u03b1-tocopherylquinone) in healthy male subjects","volume":"52","author":"Hawi","year":"2012","journal-title":"J. Clin. Pharmacol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1007\/s13311-019-00767-8","article-title":"Neuroprotective and Antioxidant Effect of Ginkgo biloba Extract Against AD and Other Neurological Disorders","volume":"16","author":"Singh","year":"2019","journal-title":"Neurotherapeutics"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"21937","DOI":"10.1074\/jbc.274.31.21937","article-title":"Potent neuroprotective properties against the Alzheimer \u03b2-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid","volume":"274","author":"Chyan","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1002\/jnr.22030","article-title":"Indole-3-propionic acid attenuates neuronal damage and oxidative stress in the ischemic hippocampus","volume":"87","author":"Hwang","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s12031-002-0036-0","article-title":"Development of indole-3-propionic acid (OXIGONTM) for Alzheimer\u2019s disease","volume":"19","author":"Bendheim","year":"2002","journal-title":"J. Mol. Neurosci."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Bernatoniene, J., and Kopustinskiene, D.M. (2018). The Role of Catechins in Cellular Responses to Oxidative Stress. Molecules, 23.","DOI":"10.3390\/molecules23040965"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"12583","DOI":"10.1038\/srep12583","article-title":"Molecular mechanisms of the non-coenzyme action of thiamin in brain: Biochemical, structural and pathway analysis","volume":"5","author":"Mkrtchyan","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"5440","DOI":"10.1007\/s12035-016-0079-9","article-title":"Thiamine Deficiency and Neurodegeneration: The Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy","volume":"54","author":"Liu","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1136\/jnnp.55.2.136","article-title":"Thiamine status in inherited degenerative ataxias","volume":"55","author":"Pedraza","year":"1992","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1017\/S0317167100052811","article-title":"Biogenic amine metabolites and thiamine in cerebrospinal fluid in heredo-degenerative ataxias","volume":"28","author":"Botez","year":"2001","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.freeradbiomed.2013.02.008","article-title":"Regulation of Nrf2-an update","volume":"66","author":"Niture","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_124","first-page":"312","article-title":"Regulation of Nrf2 Signaling","volume":"8","author":"Li","year":"2019","journal-title":"React. Oxyg. Species (Apex, NC)"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2858","DOI":"10.1016\/j.ajpath.2017.08.021","article-title":"Molecular Alterations in a Mouse Cardiac Model of Friedreich Ataxia: An Impaired Nrf2 Response Mediated via Upregulation of Keap1 and Activation of the Gsk3\u03b2 Axis","volume":"187","author":"Anzovino","year":"2017","journal-title":"Am. J. Pathol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"7853","DOI":"10.3390\/ijms14047853","article-title":"Frataxin deficiency leads to reduced expression and impaired translocation of NF-E2-related factor (Nrf2) in cultured motor neurons","volume":"14","author":"Petrini","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1089\/ars.2012.4537","article-title":"Frataxin deficiency leads to defects in expression of antioxidants and Nrf2 expression in dorsal root ganglia of the Friedreich\u2019s Ataxia YG8R mouse model","volume":"19","author":"Shan","year":"2013","journal-title":"Antioxidants Redox Signal."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"42588","DOI":"10.1074\/jbc.M301872200","article-title":"Actin glutathionylation increases in fibroblasts of patients with Friedreich\u2019s ataxia: A potential role in the pathogenesis of the disease","volume":"278","author":"Pastore","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1242\/bio.20134853","article-title":"Nrf2 impacts cellular bioenergetics by controlling substrate availability for mitochondrial respiration","volume":"2","author":"Baird","year":"2013","journal-title":"Biol. Open"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/jnc.12303","article-title":"Mitochondrial pathophysiology in Friedreich\u2019s ataxia","volume":"126","author":"Palau","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.2147\/DDDT.S193889","article-title":"Pharmacokinetics and pharmacodynamics of the novel NrF2 activator omaveloxolone in primates","volume":"13","author":"Reisman","year":"2019","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_132","first-page":"9372182","article-title":"Activators and Inhibitors of NRF2: A Review of Their Potential for Clinical Development","volume":"2019","author":"Manda","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3389\/fncel.2018.00188","article-title":"Novel Nrf2-inducer prevents mitochondrial defects and oxidative stress in friedreich\u2019s ataxia models","volume":"12","author":"Abeti","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1016\/j.biopha.2018.11.075","article-title":"Resveratrol: From enhanced biosynthesis and bioavailability to multitargeting chronic diseases","volume":"109","author":"Pannu","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Li, L., Voullaire, L., Sandi, C., Pook, M.A., and Ioannou, P.A. (2013). Pharmacological Screening Using an FXN-EGFP Cellular Genomic Reporter Assay for the Therapy of Friedreich Ataxia. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055940"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Georges, P., Boza-Moran, M.G., Gide, J., P\u00eache, G.A., For\u00eat, B., Bayot, A., Rustin, P., Peschanski, M., Martinat, C., and Aubry, L. (2019). Induced pluripotent stem cells-derived neurons from patients with Friedreich ataxia exhibit differential sensitivity to resveratrol and nicotinamide. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-49870-y"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1002\/mds.870130510","article-title":"Brain phospholipids and fatty acids in Friedreich\u2019s ataxia and spinocerebellar atrophy type-1","volume":"13","author":"Eder","year":"1998","journal-title":"Mov. Disord."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.4155\/bio.15.118","article-title":"Stable isotopes and LC-MS for monitoring metabolic disturbances in Friedreich\u2019s ataxia platelets","volume":"7","author":"Worth","year":"2015","journal-title":"Bioanalysis"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1017\/S0317167100044012","article-title":"Quantitative metabolic profiling of alpha-keto acids in Friedreich\u2019s ataxia","volume":"9","author":"Bertrand","year":"1982","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1017\/S0317167100119778","article-title":"Fatty acid profile of major lipid classes in plasma lipoproteins of patients with Friedreich\u2019s ataxia-demonstration of a low linoleic acid content most evident in the cholesterol-ester fraction","volume":"6","author":"Davignon","year":"1979","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.freeradbiomed.2014.04.016","article-title":"Frataxin deficiency in neonatal rat ventricular myocytes targets mitochondria and lipid metabolism","volume":"73","author":"Obis","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/ana.22526","article-title":"A gene expression phenotype in lymphocytes from friedreich ataxia patients","volume":"70","author":"Coppola","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1093\/hmg\/dds095","article-title":"Friedreich\u2019s ataxia reveals a mechanism for coordinate regulation of oxidative metabolism via feedback inhibition of the SIRT3 deacetylase","volume":"21","author":"Wagner","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"884S","DOI":"10.3945\/ajcn.110.001917","article-title":"Regulation of PGC-1\u03b1, a nodal regulator of mitochondrial biogenesis","volume":"93","author":"Auwerx","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1210\/er.2002-0012","article-title":"Peroxisome proliferator-activated receptor-\u03b3 coactivator 1\u03b1 (PGC-1\u03b1): Transcriptional coactivator and metabolic regulator","volume":"24","author":"Puigserver","year":"2003","journal-title":"Endocr. Rev."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.pneurobio.2017.10.002","article-title":"Peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3): A master gatekeeper in CNS injury and repair","volume":"163\u2013164","author":"Cai","year":"2018","journal-title":"Prog. Neurobiol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1210\/er.2006-0037","article-title":"Peroxisome Proliferator-Activated Receptor \u03b3 Coactivator 1 Coactivators, Energy Homeostasis, and Metabolism","volume":"27","author":"Handschin","year":"2006","journal-title":"Endocr. Rev."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.cell.2006.09.024","article-title":"Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators","volume":"127","author":"Drori","year":"2006","journal-title":"Cell"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Marmolino, D., Manto, M., Acquaviva, F., Vergara, P., Ravella, A., Monticelli, A., and Pandolfo, M. (2010). PGC-1alpha down-regulation affects the antioxidant response in Friedreich\u2019s ataxia. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010025"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.freeradbiomed.2016.06.023","article-title":"PPAR\u03b3 as a therapeutic target to rescue mitochondrial function in neurological disease","volume":"100","author":"Corona","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.cmet.2014.08.005","article-title":"Thiazolidinediones and the promise of insulin sensitization in type 2 diabetes","volume":"20","author":"Soccio","year":"2014","journal-title":"Cell Metab."},{"key":"ref_152","unstructured":"(2020, April 16). Minoryx Leriglitazone. Available online: https:\/\/www.minoryx.com\/leriglitazone\/."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Poli, S., Rodr\u00edguez-Pascau, L., Britti, E., Ros, J., Gonz\u00e1lez-Cabo, P., Lynch, D., Martinell, M., and Pizcueta, P. (May, January 25). MIN102 (Leriglitazone), a Brain Penetrant PPAR Gamma Agonist for the Treatment of Friedreich\u2019s Ataxia. Proceedings of the American Academy of Neurology 2020 Annual Meeting, Toronto, ON, Canada.","DOI":"10.1212\/WNL.94.15_supplement.4147"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1002\/mds.23711","article-title":"Could thiazolidinediones increase the risk of heart failure in Friedreich\u2019s ataxia patients?","volume":"26","author":"Pallardo","year":"2011","journal-title":"Mov. Disord."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1007\/s11064-017-2288-7","article-title":"L-Carnitine and acetyl-L-carnitine roles and neuroprotection in developing brain","volume":"42","author":"Ferreira","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1093\/hmg\/9.2.275","article-title":"Clinical, biochemical and molecular genetic correlations in Friedreich\u2019s ataxia","volume":"9","author":"Bradley","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.ajpath.2013.05.032","article-title":"Molecular and functional alterations in a mouse cardiac model of Friedreich ataxia: Activation of the integrated stress response, eIF2\u03b1 phosphorylation, and the induction of downstream targets","volume":"183","author":"Huang","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/84818","article-title":"Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits","volume":"27","author":"Puccio","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s00401-007-0220-y","article-title":"The dentate nucleus in Friedreich\u2019s ataxia: The role of iron-responsive proteins","volume":"114","author":"Koeppen","year":"2007","journal-title":"Acta Neuropathol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"130","DOI":"10.3389\/fphar.2014.00130","article-title":"Dysregulation of cellular iron metabolism in Friedreich ataxia: From primary iron-sulfur cluster deficit to mitochondrial iron accumulation","volume":"5","author":"Martelli","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"9757","DOI":"10.1073\/pnas.0804261105","article-title":"The MCK mouse heart model of Friedreich\u2019s ataxia: Alterations in iron-regulated proteins and cardiac hypertrophy are limited by iron chelation","volume":"105","author":"Whitnall","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1111\/ene.12448","article-title":"Dentate nuclei T2 relaxometry is a reliable neuroimaging marker in Friedreich\u2019s ataxia","volume":"21","author":"Bergo","year":"2014","journal-title":"Eur. J. Neurol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1136\/jnnp-2015-312665","article-title":"Tissue atrophy and elevated iron concentration in the extrapyramidal motor system in Friedreich ataxia: The IMAGE-FRDA study","volume":"87","author":"Harding","year":"2016","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"16381","DOI":"10.1073\/pnas.0906784106","article-title":"Elucidation of the mechanism of mitochondrial iron loading in Friedreich\u2019s ataxia by analysis of a mouse mutant","volume":"106","author":"Huang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"20590","DOI":"10.1073\/pnas.1215349109","article-title":"Identification of nonferritin mitochondrial iron deposits in a mouse model of Friedreich ataxia","volume":"109","author":"Whitnall","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s00702-016-1508-7","article-title":"Role of iron in neurodegenerative diseases","volume":"123","author":"Li","year":"2016","journal-title":"J. Neural Transm."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0300-483X(00)00231-6","article-title":"The Haber-Weiss reaction and mechanisms of toxicity","volume":"149","author":"Kehrer","year":"2000","journal-title":"Toxicology"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/ejh.12833","article-title":"Safety profiles of iron chelators in young patients with haemoglobinopathies","volume":"98","author":"Botzenhardt","year":"2017","journal-title":"Eur. J. Haematol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.freeradbiomed.2018.04.002","article-title":"Brain mitochondrial iron accumulates in Huntington\u2019s disease, mediates mitochondrial dysfunction, and can be removed pharmacologically","volume":"120","author":"Agrawal","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1038\/s41598-017-01402-2","article-title":"Brain iron chelation by deferiprone in a phase 2 randomised double-blinded placebo controlled clinical trial in Parkinson\u2019s disease","volume":"7","author":"Ward","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1182\/blood-2007-07-102335","article-title":"Redistribution of accumulated cell iron: A modality of chelation with therapeutic implications","volume":"111","author":"Sohn","year":"2008","journal-title":"Blood"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/jnc.12300","article-title":"Deferiprone for the treatment of Friedreich\u2019s ataxia","volume":"126","author":"Pandolfo","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"5219","DOI":"10.1182\/blood-2008-06-161919","article-title":"Cell functions impaired by frataxin deficiency are restored by drug-mediated iron relocation","volume":"112","author":"Kakhlon","year":"2008","journal-title":"Blood"},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Goncalves, S., Paupe, V., Dassa, E.P., and Rustin, P. (2008). Deferiprone targets aconitase: Implication for Friedreich\u2019s ataxia treatment. BMC Neurol., 8.","DOI":"10.1186\/1471-2377-8-20"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.ygeno.2006.06.015","article-title":"GAA repeat expansion mutation mouse models of Friedreich ataxia exhibit oxidative stress leading to progressive neuronal and cardiac pathology","volume":"88","author":"Pinto","year":"2006","journal-title":"Genomics"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.exger.2012.12.002","article-title":"Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans","volume":"48","author":"Schiavi","year":"2013","journal-title":"Exp. Gerontol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1017\/S0317167100024951","article-title":"Plasma lipids and lipoproteins in Friedreich\u2019s ataxia and familial spastic ataxia\u2014Evidence for an abnormal composition of high density lipoproteins","volume":"5","author":"Huang","year":"1978","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1136\/jnnp.43.2.111","article-title":"Lipids and lipoproteins in Friedreich\u2019s ataxia","volume":"43","author":"Walker","year":"1980","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1002\/jcb.21247","article-title":"Metabolic syndrome and mitochondrial function: Molecular replacement and antioxidant supplements to prevent membrane peroxidation and restore mitochondrial function","volume":"100","author":"Nicolson","year":"2007","journal-title":"J. Cell. Biochem."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s12031-018-1155-6","article-title":"Ferroptosis, a Recent Defined Form of Critical Cell Death in Neurological Disorders","volume":"66","author":"Wu","year":"2018","journal-title":"J. Mol. Neurosci."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.phrs.2015.05.015","article-title":"Targeting lipid peroxidation and mitochondrial imbalance in Friedreich\u2019s ataxia","volume":"99","author":"Abeti","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nchembio.2238","article-title":"Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis","volume":"13","author":"Kagan","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1093\/hmg\/ddn178","article-title":"Glutathione-dependent redox status of frataxin-deficient cells in a yeast model of Friedreich\u2019s ataxia","volume":"17","author":"Auchere","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.bbadis.2011.11.003","article-title":"Changes in mitochondrial glutathione levels and protein thiol oxidation in \u2206yfh1 yeast cells and the lymphoblasts of patients with Friedreich\u2019s ataxia","volume":"1822","author":"Bulteau","year":"2012","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1093\/hmg\/ddg187","article-title":"Decreased expression of genes involved in sulfur amino acid metabolism in frataxin-deficient cells","volume":"12","author":"Tan","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Calap-Quintana, P., Soriano, S., Llorens, J.V., Al-Ramahi, I., Botas, J., Molt\u00f3, M.D., and Mart\u00ednez-Sebasti\u00e1n, M.J. (2015). TORC1 Inhibition by Rapamycin Promotes Antioxidant Defences in a Drosophila Model of Friedreich\u2019s Ataxia. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132376"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1046\/j.1365-2362.2001.00922.x","article-title":"Glutathione in blood of patients with Friedreich\u2019s ataxia","volume":"31","author":"Piemonte","year":"2001","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/s41589-018-0031-6","article-title":"FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation","volume":"14","author":"Gaschler","year":"2018","journal-title":"Nat. Chem. Biol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/ncb3064","article-title":"Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice","volume":"16","author":"Schneider","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1007\/s10534-011-9476-8","article-title":"Glutathione: A key component of the cytoplasmic labile iron pool","volume":"24","author":"Hider","year":"2011","journal-title":"BioMetals"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41419-020-2298-2","article-title":"Ferroptosis: Past, present and future","volume":"11","author":"Li","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1124\/jpet.118.252759","article-title":"Ferroptosis as a novel therapeutic target for Friedreich\u2019s ataxia","volume":"369","author":"Xia","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Du, J., Zhou, Y., Li, Y., Xia, J., Chen, Y., Chen, S., Wang, X., Sun, W., Wang, T., and Ren, X. (2020). Identification of Frataxin as a regulator of ferroptosis. Redox Biol., 32.","DOI":"10.1016\/j.redox.2020.101483"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.bbalip.2014.10.002","article-title":"Mammalian lipoxygenases and their biological relevance","volume":"1851","author":"Kuhn","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.chembiol.2008.02.010","article-title":"Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells","volume":"15","author":"Yang","year":"2008","journal-title":"Chem. Biol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.molcel.2015.06.011","article-title":"Glutaminolysis and Transferrin Regulate Ferroptosis","volume":"59","author":"Gao","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Kahn-Kirby, A.H., Amagata, A., Maeder, C.I., Mei, J.J., Sideris, S., Kosaka, Y., Hinman, A., Malone, S.A., Bruegger, J.J., and Wang, L. (2019). Targeting ferroptosis: A novel therapeutic strategy for the treatment of mitochondrial disease-related epilepsy. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0214250"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"3693","DOI":"10.1016\/j.bmcl.2011.04.085","article-title":"\u03b1-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging","volume":"21","author":"Shrader","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ymgme.2011.10.009","article-title":"Initial experience in the treatment of inherited mitochondrial disease with EPI-743","volume":"105","author":"Enns","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_201","doi-asserted-by":"crossref","unstructured":"Lepretti, M., Martucciello, S., Alberto Burgos Aceves, M., Putti, R., and Lionetti, L. (2018). Omega-3 Fatty Acids and Insulin Resistance: Focus on the Regulation of Mitochondria and Endoplasmic Reticulum Stress. Nutrients, 10.","DOI":"10.3390\/nu10030350"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.redox.2013.06.004","article-title":"Insights into the role of oxidative stress in the pathology of friedreich ataxia using peroxidation resistant polyunsaturated fatty acids","volume":"1","author":"Cotticelli","year":"2013","journal-title":"Redox Biol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/biostatistics\/kxx069","article-title":"Estimation of clinical trial success rates and related parameters","volume":"20","author":"Wong","year":"2019","journal-title":"Biostatistics"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"e415","DOI":"10.1212\/NXG.0000000000000415","article-title":"Neurologic outcomes in Friedreich ataxia","volume":"6","author":"Pandolfo","year":"2020","journal-title":"Neurol. Genet."},{"key":"ref_205","unstructured":"Hayashi, G., Jasoliya, M., Sahdeo, S., Sacc\u00e0, F., Pane, C., Filla, A., Marsili, A., Puorro, G., Lanzillo, R., and Brescia Morra, V. (2020, March 23). Dimethyl Fumarate Mediates Nrf2-Dependent Mitochondrial Biogenesis in Mice and Humans, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6251607\/."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"5237","DOI":"10.1038\/s41598-017-04996-9","article-title":"Circulating miR-323-3p is a biomarker for cardiomyopathy and an indicator of phenotypic variability in Friedreich\u2019s ataxia patients","volume":"7","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"180021","DOI":"10.1038\/sdata.2018.21","article-title":"Small RNA-seq analysis of circulating miRNAs to identify phenotypic variability in Friedreich\u2019s ataxia patients","volume":"5","year":"2018","journal-title":"Sci. Data"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1021\/acs.analchem.7b04590","article-title":"Liquid Chromatography-High Resolution Mass Spectrometry Analysis of Platelet Frataxin as a Protein Biomarker for the Rare Disease Friedreich\u2019s Ataxia","volume":"90","author":"Guo","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"McMackin, M.Z., Durbin-Johnson, B., Napierala, M., Napierala, J.S., Ruiz, L., Napoli, E., Perlman, S., Giulivi, C., and Cortopassi, G.A. (2019). Potential biomarker identification for Friedreich\u2019s ataxia using overlapping gene expression patterns in patient cells and mouse dorsal root ganglion. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0223209"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"366","DOI":"10.3389\/fncel.2018.00366","article-title":"Plasma Markers of Neurodegeneration Are Raised in Friedreich\u2019s Ataxia","volume":"12","author":"Zeitlberger","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"FSO398","DOI":"10.2144\/fsoa-2019-0026","article-title":"The current state of biomarker research for Friedreich\u2019s ataxia: A report from the 2018 FARA biomarker meeting","volume":"5","author":"Blair","year":"2019","journal-title":"Futur. Sci. OA"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1002\/1873-3468.12928","article-title":"The role of oxidative stress in Friedreich\u2019s ataxia","volume":"592","author":"Lupoli","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.bbrc.2012.01.022","article-title":"Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells","volume":"418","author":"Lefevre","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1096\/fj.05-5709com","article-title":"Causative role of oxidative stress in a Drosophila model of Friedreich ataxia","volume":"21","author":"Llorens","year":"2007","journal-title":"FASEB J."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1093\/hmg\/11.7.815","article-title":"Frataxin promotes antioxidant defense in a thiol-dependent manner resulting in diminished malignant transformation in vitro","volume":"11","author":"Shoichet","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"Jasoliya, M., Sacca, F., Sahdeo, S., Chedin, F., Pane, C., Brescia Morra, V., Filla, A., Pook, M., and Cortopassi, G. (2019). Dimethyl fumarate dosing in humans increases frataxin expression: A potential therapy for Friedreich\u2019s Ataxia. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0217776"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.mito.2006.05.002","article-title":"Mitochondrial disease activates transcripts of the unfolded protein response and cell cycle and inhibits vesicular secretion and oligodendrocyte-specific transcripts","volume":"6","author":"Cortopassi","year":"2006","journal-title":"Mitochondrion"},{"key":"ref_218","doi-asserted-by":"crossref","unstructured":"Edenharter, O., Schneuwly, S., and Navarro, J.A. (2018). Mitofusin-Dependent ER Stress Triggers Glial Dysfunction and Nervous System Degeneration in a Drosophila Model of Friedreich\u2019s Ataxia. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00038"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"NS20180061","DOI":"10.1042\/NS20180061","article-title":"Mitochondrial calcium signalling and neurodegenerative diseases","volume":"2","author":"Britti","year":"2018","journal-title":"Neuronal Signal."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.bbadis.2017.12.005","article-title":"Mitochondrial pore opening and loss of Ca2+ exchanger NCLX levels occur after frataxin depletion","volume":"1864","author":"Purroy","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.18632\/aging.101247","article-title":"Friedreich\u2019s ataxia induced pluripotent stem cell-derived cardiomyocytes display electrophysiological abnormalities and calcium handling deficiency","volume":"9","author":"Crombie","year":"2017","journal-title":"Aging (Albany NY)"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1093\/hmg\/8.3.425","article-title":"The Friedreich\u2019s ataxia mutation confers cellular sensitivity to oxidant stress which is rescued by chelators of iron and calcium and inhibitors of apoptosis","volume":"8","author":"Wong","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1016\/j.cub.2015.05.059","article-title":"Iron-Starvation-Induced Mitophagy Mediates Lifespan Extension upon Mitochondrial Stress in C. elegans","volume":"25","author":"Schiavi","year":"2015","journal-title":"Curr. Biol."},{"key":"ref_224","doi-asserted-by":"crossref","unstructured":"Monnier, V., Llorens, J., and Navarro, J. (2018). Impact of Drosophila Models in the Study and Treatment of Friedreich\u2019s Ataxia. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19071989"},{"key":"ref_225","doi-asserted-by":"crossref","unstructured":"Soriano, S., Calap-Quintana, P., Llorens, J.V., Al-Ramahi, I., Guti\u00e9rrez, L., Mart\u00ednez-Sebasti\u00e1n, M.J., Botas, J., and Molt\u00f3, M.D. (2016). Metal Homeostasis Regulators Suppress FRDA Phenotypes in a Drosophila Model of the Disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0159209"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s12311-012-0383-5","article-title":"Friedreich\u2019s ataxia causes redistribution of iron, copper, and zinc in the dentate nucleus","volume":"11","author":"Koeppen","year":"2012","journal-title":"Cerebellum"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/nm.3510","article-title":"Prevention and reversal of severe mitochondrial cardiomyopathy by gene therapy in a mouse model of Friedreich\u2019s ataxia","volume":"20","author":"Perdomini","year":"2014","journal-title":"Nat. Med."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1016\/j.ymthe.2018.05.006","article-title":"Rapid and Complete Reversal of Sensory Ataxia by Gene Therapy in a Novel Model of Friedreich Ataxia","volume":"26","author":"Piguet","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1089\/hum.2013.180","article-title":"Cell and Gene Therapy for Friedreich Ataxia: Progress to Date","volume":"25","author":"Dottori","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"261","DOI":"10.5348\/ijcri-201503-CS-10054","article-title":"A novel approach of human embryonic stem cells therapy in treatment of Friedrich\u2019s Ataxia","volume":"6","author":"Shroff","year":"2015","journal-title":"Int. J. Case Rep. Images"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/8\/664\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:51:34Z","timestamp":1760176294000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/8\/664"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,24]]},"references-count":230,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["antiox9080664"],"URL":"https:\/\/doi.org\/10.3390\/antiox9080664","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,24]]}}}