{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T08:46:32Z","timestamp":1770885992705,"version":"3.50.1"},"reference-count":87,"publisher":"Oxford University Press (OUP)","issue":"22","license":[{"start":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T00:00:00Z","timestamp":1606176000000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Ministero della Istruzione Universit\u00e0 e Ricerca","award":["RBFR131WDS-001"],"award-info":[{"award-number":["RBFR131WDS-001"]}]},{"name":"Ministero della Istruzione Universit\u00e0 e Ricerca","award":["RBFR131WDS-002"],"award-info":[{"award-number":["RBFR131WDS-002"]}]},{"name":"Italian Ministry of Health"},{"name":"Fondazione Veronesi"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>OPA1 mutations are the major cause of dominant optic atrophy (DOA) and the syndromic form DOA plus, pathologies for which there is no established cure. We used a \u2018drug repurposing\u2019 approach to identify FDA-approved molecules able to rescue the mitochondrial dysfunctions induced by OPA1 mutations. We screened two different chemical libraries by using two yeast strains carrying the mgm1I322M and the chim3P646L mutations, identifying 26 drugs able to rescue their oxidative growth phenotype. Six of them, able to reduce the mitochondrial DNA instability in yeast, have been then tested in Opa1 deleted mouse embryonic fibroblasts expressing the human OPA1 isoform 1 bearing the R445H and D603H mutations. Some of these molecules were able to ameliorate the energetic functions and\/or the mitochondrial network morphology, depending on the type of OPA1 mutation. The final validation has been performed in patients\u2019 fibroblasts, allowing to select the most effective molecules. Our current results are instrumental to rapidly translating the findings of this drug repurposing approach into clinical trial for DOA and other neurodegenerations caused by OPA1 mutations.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa244","type":"journal-article","created":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T20:36:28Z","timestamp":1605904588000},"page":"3631-3645","source":"Crossref","is-referenced-by-count":15,"title":["Drug repositioning as a therapeutic strategy for neurodegenerations associated with <i>OPA1<\/i> mutations"],"prefix":"10.1093","volume":"29","author":[{"given":"Serena J","family":"Aleo","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna 40126, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Del Dotto","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna 40139, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Fogazza","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna 40126, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Maresca","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna 40139, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziana","family":"Lodi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Life Science and Environmental Sustainability, University of Parma, Parma 43124, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Goffrini","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Life Science and Environmental Sustainability, University of Parma, Parma 43124, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Ghelli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna 40126, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Rugolo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna 40126, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerio","family":"Carelli","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna 40139, Italy"},{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna 40139, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8280-7849","authenticated-orcid":false,"given":"Enrico","family":"Baruffini","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Life Science and Environmental Sustainability, University of Parma, Parma 43124, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Zanna","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna 40126, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,11,24]]},"reference":[{"key":"2021012301195711500_ref1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1042\/EBC20170104","article-title":"Mitochondrial dynamics: overview of molecular mechanisms","volume":"62","author":"Tilokani","year":"2018","journal-title":"Essays Biochem."},{"key":"2021012301195711500_ref2","doi-asserted-by":"crossref","first-page":"e50973","DOI":"10.7554\/eLife.50973","article-title":"Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane","volume":"9","author":"Ge","year":"2020","journal-title":"Elife"},{"key":"2021012301195711500_ref3","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1038\/ncb3560","article-title":"Molecular basis of selective mitochondrial fusion by heterotypic action between OPA1 and cardiolipin","volume":"19","author":"Ban","year":"2017","journal-title":"Nat. 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