{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:04:02Z","timestamp":1791306242735,"version":"4.3.1"},"reference-count":61,"publisher":"The Company of Biologists","issue":"7","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":1891,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Muscle mass wasting is one of the most debilitating symptoms of myotonic dystrophy type 1 (DM1) disease, ultimately leading to immobility, respiratory defects, dysarthria, dysphagia and death in advanced stages of the disease. In order to study the molecular mechanisms leading to the degenerative loss of adult muscle tissue in DM1, we generated an inducible Drosophila model of expanded CTG trinucleotide repeat toxicity that resembles an adult-onset form of the disease. Heat-shock induced expression of 480 CUG repeats in adult flies resulted in a reduction in the area of the indirect flight muscles. In these model flies, reduction of muscle area was concomitant with increased apoptosis and autophagy. Inhibition of apoptosis or autophagy mediated by the overexpression of DIAP1, mTOR (also known as Tor) or muscleblind, or by RNA interference (RNAi)-mediated silencing of autophagy regulatory genes, achieved a rescue of the muscle-loss phenotype. In fact, mTOR overexpression rescued muscle size to a size comparable to that in control flies. These results were validated in skeletal muscle biopsies from DM1 patients in which we found downregulated autophagy and apoptosis repressor genes, and also in DM1 myoblasts where we found increased autophagy. These findings provide new insights into the signaling pathways involved in DM1 disease pathogenesis.<\/jats:p>","DOI":"10.1242\/dmm.018127","type":"journal-article","created":{"date-parts":[[2015,6,18]],"date-time":"2015-06-18T14:46:17Z","timestamp":1434638777000},"page":"679-690","source":"Crossref","is-referenced-by-count":75,"title":["Increased autophagy and apoptosis contribute to muscle atrophy in a myotonic dystrophy type 1 <i>Drosophila<\/i> model"],"prefix":"10.1242","volume":"8","author":[{"given":"Ariadna","family":"Bargiela","sequence":"first","affiliation":[{"name":"Translational Genomics Group, Department of Genetics, University of Valencia, Burjassot 46100, Spain"},{"name":"INCLIVA Health Research Institute, Valencia 46010, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefan\u00eda","family":"Cerro-Herreros","sequence":"additional","affiliation":[{"name":"Translational Genomics Group, Department of Genetics, University of Valencia, Burjassot 46100, Spain"},{"name":"INCLIVA Health Research Institute, Valencia 46010, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan M.","family":"Fernandez-Costa","sequence":"additional","affiliation":[{"name":"Translational Genomics Group, Department of Genetics, University of Valencia, Burjassot 46100, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Vilchez","sequence":"additional","affiliation":[{"name":"Neurology Section, Hospital Universitari La Fe, Valencia 46026, Spain"},{"name":"Department of Internal Medicine, University of Valencia, Valencia 46010, Spain"},{"name":"Centro de Investigaciones Biomedicas en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Madrid 28049, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Llamusi","sequence":"additional","affiliation":[{"name":"INCLIVA Health Research Institute, Valencia 46010, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Artero","sequence":"additional","affiliation":[{"name":"Translational Genomics Group, Department of Genetics, University of Valencia, Burjassot 46100, Spain"},{"name":"INCLIVA Health Research Institute, Valencia 46010, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042501204559800_DMM018127C1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.semcdb.2015.02.001","article-title":"Cell death in development: signaling pathways and core mechanisms","volume":"39","author":"Arya","year":"2015","journal-title":"Semin. 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