{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:03:01Z","timestamp":1791565381345,"version":"4.3.4"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"24","license":[{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"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\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R21NS107918-01A1"],"award-info":[{"award-number":["1R21NS107918-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Previously we showed that dimethyl fumarate (DMF) dose-dependently increased mitochondrial gene expression and function in cells and might be considered as a therapeutic for inherited mitochondrial disease, including Friedreich\u2019s ataxia (FA). Here we tested DMF\u2019s ability to dose-dependently increase mitochondrial function, mitochondrial gene expression (frataxin and cytochrome oxidase protein) and mitochondrial copy number in C57BL6 wild-type mice and the FXNKD mouse model of FA. We first dosed DMF at 0\u2013320\u00a0mg\/kg in C57BL6 mice and observed significant toxicity above 160\u00a0mg\/kg orally, defining the maximum tolerated dose. Oral dosing of C57BL6 mice in the range 0\u2013160\u00a0mg\/kg identified a maximum increase in aconitase activity and mitochondrial gene expression in brain and quadriceps at 110\u00a0mg\/kg DMF, thus defining the maximum effective dose (MED). The MED of DMF in mice overlaps the currently approved human-equivalent doses of DMF prescribed for multiple sclerosis (480\u00a0mg\/day) and psoriasis (720\u00a0mg\/day). In the FXNKD mouse model of FA, which has a doxycycline-induced deficit of frataxin protein, we observed significant decreases of multiple mitochondrial parameters, including deficits in brain mitochondrial Complex 2, Complex 4 and aconitase activity, supporting the idea that frataxin deficiency reduces mitochondrial gene expression, mitochondrial functions and biogenesis. About 110\u00a0mg\/kg of oral DMF rescued these enzyme activities in brain and rescued frataxin and cytochrome oxidase expression in brain, cerebellum and quadriceps muscle of the FXNKD mouse model. Taken together, these results support the idea of using fumarate-based molecules to treat FA or other mitochondrial diseases.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa282","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T07:22:14Z","timestamp":1610090534000},"page":"3954-3965","source":"Crossref","is-referenced-by-count":31,"title":["Dimethyl fumarate dose-dependently increases mitochondrial gene expression and function in muscle and brain of Friedreich\u2019s ataxia model mice"],"prefix":"10.1093","volume":"29","author":[{"given":"Chun Kiu","family":"Hui","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena N","family":"Dedkova","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gino","family":"Cortopassi","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"2021100109413743700_ref1","doi-asserted-by":"crossref","first-page":"7452","DOI":"10.1073\/pnas.94.14.7452","article-title":"Evolution of the Friedreich's ataxia trinucleotide repeat expansion: founder effect and permutations","volume":"94","author":"Cossee","year":"1997","journal-title":"Proc. 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