{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:52:51Z","timestamp":1790779971904,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T00:00:00Z","timestamp":1671753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003768","name":"Universit\u00e9 de Strasbourg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003768","id-type":"DOI","asserted-by":"crossref"}]},{"name":"IdEx Unistra","award":["ANR-10-IDEX-0002"],"award-info":[{"award-number":["ANR-10-IDEX-0002"]}]},{"name":"AFM-T\u00e9l\u00e9thon"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Congenital myopathies define a genetically heterogeneous group of disorders associated with severe muscle weakness, for which no therapies are currently available. Here we investigated the repurposing of tamoxifen in mouse models of mild or severe forms of centronuclear myopathies due to mutations in BIN1 (encoding amphiphysin 2) or DNM2 (encoding dynamin 2), respectively. Exposure to a tamoxifen-enriched diet from 3 weeks of age resulted in significant improvement in muscle contractility without increase in fibre size in both models, underlying an increase in the capacity of the muscle fibres to produce more force. In addition, the histological alterations were fully rescued in the BIN1-centronuclear myopathies mouse model. To assess the mechanism of the rescue, transcriptome analyses and targeted protein studies were performed.<\/jats:p>\n               <jats:p>Although tamoxifen is known to modulate the transcriptional activity of the oestrogen receptors, correction of the disease transcriptomic signature was marginal on tamoxifen treatment. Conversely, tamoxifen lowered the abnormal increase in dynamin 2 protein level in both centronuclear myopathies models. Of note, it was previously reported that dynamin 2 increase is a main pathological cause of centronuclear myopathies. The Akt\/mTOR muscle hypertrophic pathway and protein markers of the ubiquitin\u2013proteasome system (the E3 ubiquitin ligase cullin 3) and autophagy (p62) were increased in both models of centronuclear myopathies. Normalization of dynamin 2 level mainly correlated with the normalization of cullin 3 protein level on tamoxifen treatment, supporting the idea that the ubiquitin\u2013proteasome system is a main target for the tamoxifen effect in the amelioration of these diseases. Overall, our data suggest that tamoxifen antagonizes disease development probably through dynamin 2 level regulation. In conclusion, the beneficial effect of tamoxifen on muscle function supports the suggestion that tamoxifen may serve as a common therapy for several autosomal forms of centronuclear myopathies.<\/jats:p>","DOI":"10.1093\/brain\/awac489","type":"journal-article","created":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T08:06:53Z","timestamp":1671782813000},"page":"3029-3048","source":"Crossref","is-referenced-by-count":19,"title":["Tamoxifen improves muscle structure and function of <i>Bin1<\/i>- and <i>Dnm2<\/i>-related centronuclear myopathies"],"prefix":"10.1093","volume":"146","author":[{"given":"Charlotte","family":"Gineste","sequence":"first","affiliation":[{"name":"Department of Translational Medicine and Neurogenetics, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), Inserm U1258, CNRS UMR7104, Strasbourg University , Illkirch 67404 , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alix","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Neurogenetics, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), Inserm U1258, CNRS UMR7104, Strasbourg University , Illkirch 67404 , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Neurogenetics, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), Inserm U1258, CNRS UMR7104, Strasbourg University , Illkirch 67404 , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Reiss","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Neurogenetics, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), Inserm U1258, CNRS UMR7104, Strasbourg University , Illkirch 67404 , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8256-5862","authenticated-orcid":false,"given":"Jocelyn","family":"Laporte","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Neurogenetics, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), Inserm U1258, CNRS UMR7104, Strasbourg University , Illkirch 67404 , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,23]]},"reference":[{"key":"2023070312510477500_awac489-B1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.nmd.2008.04.002","article-title":"What's new in congenital myopathies?","volume":"18","author":"North","year":"2008","journal-title":"Neuromuscul 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