{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:56:45Z","timestamp":1793501805972,"version":"4.5.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:00:00Z","timestamp":1674691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008475","name":"Brunel University London","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008475","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002108","name":"Friedreich\u2019s Ataxia Research Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Friedreich\u2019s ataxia (FRDA) is an inherited recessive neurodegenerative disorder caused by a homozygous guanine-adenine-adenine (GAA) repeat expansion within intron 1 of the <jats:italic>FXN<\/jats:italic> gene, which encodes the essential mitochondrial protein frataxin. There is still no effective therapy for FRDA, therefore the development of optimal cell and animal models of the disease is one of the priorities for preclinical therapeutic testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We obtained the latest FRDA humanized mouse model that was generated on the basis of our previous YG8sR, by Jackson laboratory [YG8JR, <jats:italic>Fxn<\/jats:italic><jats:sup>null<\/jats:sup>:YG8s(GAA) &amp;gt; 800]. We characterized the behavioral, cellular, molecular and epigenetics properties of the YG8JR model, which has the largest GAA repeat sizes compared to all the current FRDA mouse models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found statistically significant behavioral deficits, together with reduced levels of frataxin mRNA and protein, and aconitase activity in YG8JR mice compared with control Y47JR mice. YG8JR mice exhibit intergenerational GAA repeat instability by the analysis of parent and offspring tissue samples. Somatic GAA repeat instability was also detected in individual brain and cerebellum tissue samples. In addition, increased DNA methylation of CpG U13 was identified in <jats:italic>FXN<\/jats:italic> GAA repeat region in the brain, cerebellum, and heart tissues. Furthermore, we show decreased histone H3K9 acetylation and increased H3K9 methylation of YG8JR cerebellum tissues within the <jats:italic>FXN<\/jats:italic> gene, upstream and downstream of the GAA repeat region compared to Y47JR controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These studies provide a detailed characterization of the GAA repeat expansion-based YG8JR transgenic mouse models that will help investigations of FRDA disease mechanisms and therapy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2023.930422","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T10:14:05Z","timestamp":1674728045000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["A new FRDA mouse model [Fxnnull:YG8s(GAA) &gt; 800] with more than 800 GAA repeats"],"prefix":"10.3389","volume":"17","author":[{"given":"Ester","family":"Kalef-Ezra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred Jonathan","family":"Edzeamey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adamo","family":"Valle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Khonsari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Kleine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Oggianu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Al-Mahdawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Pook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Anjomani Virmouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","doi-asserted-by":"publisher","first-page":"e2237","DOI":"10.1038\/cddis.2016.111","article-title":"Mitochondrial energy imbalance and lipid peroxidation cause cell death in Friedreich\u2019s ataxia.","volume":"7","author":"Abeti","year":"2016","journal-title":"Cell Death Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1093\/hmg\/ddm346","article-title":"The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues.","volume":"17","author":"Al-Mahdawi","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.ygeno.2004.04.003","article-title":"GAA repeat instability in Friedreich ataxia YAC transgenic mice.","volume":"84","author":"Al-Mahdawi","year":"2004","journal-title":"Genomics"},{"key":"B5","doi-asserted-by":"publisher","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":"Al-Mahdawi","year":"2006","journal-title":"Genomics"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e74956","DOI":"10.1371\/journal.pone.0074956","article-title":"Friedreich ataxia patient tissues exhibit increased 5-hydroxymethylcytosine modification and decreased CTCF binding at the FXN locus.","volume":"8","author":"Al-Mahdawi","year":"2013","journal-title":"PLoS One"},{"key":"B7","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s13024-015-0019-6","article-title":"Identification of telomere dysfunction in Friedreich ataxia.","volume":"10","author":"Anjomani Virmouni","year":"","journal-title":"Mol. Neurodegener."},{"key":"B8","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1242\/dmm.018952","article-title":"A novel GAA-repeat-expansion-based mouse model of Friedreich\u2019s ataxia.","volume":"8","author":"Anjomani Virmouni","year":"","journal-title":"Dis. Model. Mech."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e107416","DOI":"10.1371\/journal.pone.0107416","article-title":"Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich ataxia.","volume":"9","author":"Anjomani Virmouni","year":"2014","journal-title":"PLoS One"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1126\/science.276.5319.1709","article-title":"Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin.","volume":"276","author":"Babcock","year":"1997","journal-title":"Science"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e47085","DOI":"10.1371\/journal.pone.0047085","article-title":"Pms2 suppresses large expansions of the (GAA\u22c5TTC)n sequence in neuronal tissues.","volume":"7","author":"Bourn","year":"2012","journal-title":"PLoS One"},{"key":"B12","doi-asserted-by":"publisher","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":"B13","doi-asserted-by":"publisher","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":"B14","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1136\/jmg.2008.058594","article-title":"DNA methylation in intron 1 of the frataxin gene is related to GAA repeat length and age of onset in Friedreich ataxia patients.","volume":"45","author":"Castaldo","year":"2008","journal-title":"J. Med. Genet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1089\/ars.2012.5009","article-title":"Can telomere shortening in human peripheral blood leukocytes serve as a disease biomarker of Friedreich\u2019s ataxia?","volume":"18","author":"Castaldo","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1136\/jnnp.45.12.1136","article-title":"Studies of cellular hypersensitivity to ionising radiation in Friedreich\u2019s ataxia.","volume":"45","author":"Chamberlain","year":"1982","journal-title":"J. Neurol. Neurosurg. Psychiatr."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2662","DOI":"10.1093\/hmg\/ddt115","article-title":"Heterochromatinization induced by GAA-repeat hyperexpansion in Friedreich\u2019s ataxia can be reduced upon HDAC inhibition by vitamin B3.","volume":"22","author":"Chan","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e30054","DOI":"10.7554\/eLife.30054","article-title":"Inducible and reversible phenotypes in a novel mouse model of Friedreich\u2019s Ataxia.","volume":"6","author":"Chandran","year":"2017","journal-title":"eLife"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e16043","DOI":"10.7554\/eLife.16043","article-title":"Loss of Frataxin induces iron toxicity, sphingolipid synthesis, and Pdk1\/Mef2 activation, leading to neurodegeneration.","volume":"5","author":"Chen","year":"2016","journal-title":"eLife"},{"key":"B20","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.omtn.2018.04.009","article-title":"Increased frataxin expression induced in Friedreich ataxia cells by platinum TALE-VP64s or platinum TALE-SunTag.","volume":"12","author":"Cherif","year":"2018","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e0138437","DOI":"10.1371\/journal.pone.0138437","article-title":"FXN promoter silencing in the humanized mouse model of Friedreich ataxia.","volume":"10","author":"Chutake","year":"2015","journal-title":"PLoS One"},{"key":"B22","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1007\/s00439-006-0249-3","article-title":"The GAA triplet-repeat is unstable in the context of the human FXN locus and displays age-dependent expansions in cerebellum and DRG in a transgenic mouse model.","volume":"120","author":"Clark","year":"2007","journal-title":"Hum. Genet."},{"key":"B23","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1093\/bmb\/ldx034","article-title":"Friedreich\u2019s ataxia: clinical features, pathogenesis and management.","volume":"124","author":"Cook","year":"2017","journal-title":"Br. Med. Bull."},{"key":"B24","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1002\/ana.21052","article-title":"Progressive GAA expansions in dorsal root ganglia of Friedreich\u2019s ataxia patients.","volume":"61","author":"De Biase","year":"","journal-title":"Ann. Neurol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ygeno.2007.04.001","article-title":"Somatic instability of the expanded GAA triplet-repeat sequence in Friedreich ataxia progresses throughout life.","volume":"90","author":"De Biase","year":"","journal-title":"Genomics"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1093\/hmg\/7.12.1901","article-title":"Parental gender, age at birth and expansion length influence GAA repeat intergenerational instability in the X25 gene: pedigree studies and analysis of sperm from patients with Friedreich\u2019s ataxia.","volume":"7","author":"De Michele","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"B27","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/1531-8249(199905)45:5<673::AID-ANA20>3.0.CO;2-Q","article-title":"Direct evidence that mitochondrial iron accumulation occurs in Friedreich ataxia.","volume":"45","author":"Delatycki","year":"1999","journal-title":"Ann. Neurol."},{"key":"B28","doi-asserted-by":"publisher","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":"B29","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":"B30","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1038\/sj.embor.embor918","article-title":"An interaction between frataxin and Isu1\/Nfs1 that is crucial for Fe\/S cluster synthesis on Isu1.","volume":"4","author":"Gerber","year":"2003","journal-title":"EMBO Rep."},{"key":"B31","doi-asserted-by":"publisher","first-page":"5351","DOI":"10.1093\/nar\/gkm589","article-title":"A persistent RNA.DNA hybrid formed by transcription of the Friedreich ataxia triplet repeat in live bacteria, and by T7 RNAP in vitro.","volume":"35","author":"Grabczyk","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"B32","doi-asserted-by":"crossref","first-page":"3383","DOI":"10.1093\/nar\/gkm271","article-title":"Repeat-induced epigenetic changes in intron 1 of the frataxin gene and its consequences in Friedreich ataxia.","volume":"35","author":"Greene","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1093\/brain\/104.3.589","article-title":"Friedreich\u2019s ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features.","volume":"104","author":"Harding","year":"1981","journal-title":"Brain"},{"key":"B34","doi-asserted-by":"crossref","first-page":"6838","DOI":"10.1093\/hmg\/ddu407","article-title":"Frataxin deficiency increases cyclooxygenase 2 and prostaglandins in cell and animal models of Friedreich\u2019s ataxia.","volume":"23","author":"Hayashi","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"B35","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/nchembio815","article-title":"Histone deacetylase inhibitors reverse gene silencing in Friedreich\u2019s ataxia.","volume":"2","author":"Herman","year":"2006","journal-title":"Nat. Chem. Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"683","DOI":"10.2144\/000112597","article-title":"MethylScreen: DNA methylation density monitoring using quantitative PCR.","volume":"43","author":"Holemon","year":"2007","journal-title":"BioTechniques"},{"key":"B37","doi-asserted-by":"publisher","first-page":"182","DOI":"10.2144\/000113615","article-title":"Detection of interruptions in the GAA trinucleotide repeat expansion in the FXN gene of Friedreich ataxia.","volume":"50","author":"Holloway","year":"2011","journal-title":"BioTechniques"},{"key":"B38","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1002\/ana.25207","article-title":"Bone marrow transplantation stimulates neural repair in Friedreich\u2019s ataxia mice.","volume":"83","author":"Kemp","year":"2018","journal-title":"Ann. Neurol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1038\/gt.2016.61","article-title":"Lentivirus-meditated frataxin gene delivery reverses genome instability in Friedreich ataxia patient and mouse model fibroblasts.","volume":"23","author":"Khonsari","year":"2016","journal-title":"Gene Ther."},{"key":"B40","doi-asserted-by":"publisher","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":"B41","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/ng0897-345","article-title":"Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin.","volume":"16","author":"Koutnikova","year":"1997","journal-title":"Nat. Genet."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e55940","DOI":"10.1371\/journal.pone.0055940","article-title":"Pharmacological screening using an FXN-EGFP cellular genomic reporter assay for the therapy of Friedreich ataxia.","volume":"8","author":"Li","year":"2013","journal-title":"PLoS One"},{"key":"B43","doi-asserted-by":"publisher","first-page":"6932","DOI":"10.1093\/hmg\/ddv397","article-title":"Expanded GAA repeats impede transcription elongation through the FXN gene and induce transcriptional silencing that is restricted to the FXN locus.","volume":"24","author":"Li","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e0189990","DOI":"10.1371\/journal.pone.0189990","article-title":"Somatic instability of the expanded GAA repeats in Friedreich\u2019s ataxia.","volume":"12","author":"Long","year":"2017","journal-title":"PLoS One"},{"key":"B45","doi-asserted-by":"publisher","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":"B46","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1212\/01.wnl.0000073537.08141.77","article-title":"GAA expansion size and age at onset of Friedreich\u2019s ataxia.","volume":"61","author":"Mateo","year":"2003","journal-title":"Neurology"},{"key":"B47","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1007\/s13311-018-00706-z","article-title":"Phosphodiesterase inhibitors revert axonal dystrophy in friedreich\u2019s ataxia mouse model.","volume":"16","author":"Moll\u00e1","year":"2019","journal-title":"Neurotherapeutics"},{"key":"B48","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1242\/dmm.024273","article-title":"Two different pathogenic mechanisms, dying-back axonal neuropathy and pancreatic senescence, are present in the YG8R mouse model of Friedreich\u2019s ataxia.","volume":"9","author":"Moll\u00e1","year":"2016","journal-title":"Dis. Model. Mech."},{"key":"B49","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1212\/wnl.49.2.606","article-title":"Somatic mosaicism for Friedreich\u2019s ataxia GAA triplet repeat expansions in the central nervous system.","volume":"49","author":"Montermini","year":"1997","journal-title":"Neurology"},{"key":"B50","doi-asserted-by":"publisher","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":"B51","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/gt.2016.89","article-title":"Deletion of the GAA repeats from the human frataxin gene using the CRISPR-Cas9 system in YG8R-derived cells and mouse models of Friedreich ataxia.","volume":"24","author":"Ouellet","year":"2017","journal-title":"Gene Ther."},{"key":"B52","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/jnc.12219","article-title":"Animal and cellular models of Friedreich ataxia.","volume":"126","author":"Perdomini","year":"2013","journal-title":"J. Neurochem."},{"key":"B53","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s100480100118","article-title":"Rescue of the Friedreich\u2019s ataxia knockout mouse by human YAC transgenesis.","volume":"3","author":"Pook","year":"2001","journal-title":"Neurogenetics"},{"key":"B54","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/ng1097-215","article-title":"Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia.","volume":"17","author":"R\u00f6tig","year":"1997","journal-title":"Nat. Genet."},{"key":"B55","doi-asserted-by":"publisher","first-page":"6848","DOI":"10.1093\/hmg\/ddu408","article-title":"Dyclonine rescues frataxin deficiency in animal models and buccal cells of patients with Friedreich\u2019s ataxia.","volume":"23","author":"Sahdeo","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"B56","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/s1097-2765(00)80474-8","article-title":"Sticky DNA: self-association properties of long GAA.TTC repeats in R.R.Y triplex structures from Friedreich\u2019s ataxia.","volume":"3","author":"Sakamoto","year":"1999","journal-title":"Mol. Cell"},{"key":"B57","doi-asserted-by":"publisher","first-page":"852080","DOI":"10.1155\/2013\/852080","article-title":"Epigenetics in friedreich\u2019s ataxia: challenges and opportunities for therapy.","volume":"2013","author":"Sandi","year":"2013","journal-title":"Genet. Res. Int."},{"key":"B58","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.nbd.2011.02.016","article-title":"Prolonged treatment with pimelic o-aminobenzamide HDAC inhibitors ameliorates the disease phenotype of a Friedreich ataxia mouse model.","volume":"42","author":"Sandi","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"B59","doi-asserted-by":"publisher","first-page":"e89488","DOI":"10.1371\/journal.pone.0089488","article-title":"Generation and characterisation of Friedreich ataxia YG8R mouse fibroblast and neural stem cell models.","volume":"9","author":"Sandi","year":"2014","journal-title":"PLoS One"},{"key":"B60","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1093\/hmg\/ddy016","article-title":"Effect of diazoxide on Friedreich ataxia models.","volume":"27","author":"Santoro","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"B61","doi-asserted-by":"publisher","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":"B62","doi-asserted-by":"publisher","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":"Antioxid. Redox Signal."},{"key":"B63","doi-asserted-by":"publisher","first-page":"3457","DOI":"10.1093\/hmg\/ddv096","article-title":"Expanded GAA repeats impair FXN gene expression and reposition the FXN locus to the nuclear lamina in single cells.","volume":"24","author":"Silva","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"B64","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.pjnns.2018.02.003","article-title":"Progress in the treatment of Friedreich ataxia.","volume":"52","author":"Tai","year":"2018","journal-title":"Neurol. Neurochir. Pol."},{"key":"B65","doi-asserted-by":"publisher","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."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2023.930422\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T10:14:14Z","timestamp":1674728054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2023.930422\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,26]]},"references-count":65,"alternative-id":["10.3389\/fnins.2023.930422"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2023.930422","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,26]]},"article-number":"930422"}}