{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:35:31Z","timestamp":1777451731477,"version":"3.51.4"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T00:00:00Z","timestamp":1628812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31371060"],"award-info":[{"award-number":["31371060"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["#31871201"],"award-info":[{"award-number":["#31871201"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Friedreich ataxia (FRDA) is a serious hereditary neurodegenerative disease, mostly accompanied with hypertrophic cardiomyopathy, caused by the reduced expression of frataxin (FXN). However, there is still no effective treatment. Our previous studies have shown that SS-31, a mitochondrion-targeted peptide, is capable to upregulate the expression of FXN and improve the mitochondrial function in cells derived from FRDA patients. To further explore the potential of SS-31, we used the GAA expansion-based models, including Y47 and YG8R (Fxn KIKO) mice, primary neurons and macrophages from the mice and cells derived from FRDA patients. After once-daily intraperitoneal injection of 1\u00a0mg\/kg SS-31 for 1 month, we observed the significant improvement of motor function. The vacuolation in dorsal root ganglia, lesions in dentate nuclei and the lost thickness of myelin sheath of spinal cord were all repaired after SS-31 treatment. In addition, the hypertrophic cardiomyocytes and disarrayed abnormal Purkinje cells were dramatically reduced. Interestingly, we found that SS-31 treatment upregulated FXN expression not only at the translational levels as observed in cell culture but also at mRNA levels in vivo. Consequently, mitochondrial morphology and function were greatly improved in all tested tissues. Importantly, our data provided additional evidence that the maintenance of the therapeutic benefits needed continuous drug administration. Taken together, our findings have demonstrated the effectiveness of SS-31 treatment through the upregulation of FXN in vivo and offer guidance of the potential usage in the clinical application for FRDA.<\/jats:p>","DOI":"10.1093\/hmg\/ddab232","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T11:09:10Z","timestamp":1628593750000},"page":"176-188","source":"Crossref","is-referenced-by-count":14,"title":["SS-31 efficacy in a mouse model of Friedreich ataxia by upregulation of frataxin expression"],"prefix":"10.1093","volume":"31","author":[{"given":"Yutong","family":"Liu","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaqi","family":"Shen","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weichen","family":"Dong","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China"},{"name":"Department of Neurology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Xu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maoxin","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Life Sciences, Nanjing University, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yishan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Life Sciences, Nanjing University, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiali","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yibing","family":"Ding","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9738-049X","authenticated-orcid":false,"given":"Kuanyu","family":"Li","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,8,13]]},"reference":[{"key":"2022010913473957200_ref1","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":"2022010913473957200_ref2","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1001\/archneur.56.10.1201","article-title":"Molecular pathogenesis of Friedreich ataxia","volume":"56","author":"Pandolfo","year":"1999","journal-title":"Arch. 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