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While these drugs are generally safe, treatment adherence is not optimal in a considerable proportion of patients because of the adverse effects on skeletal muscles in the forms of myopathy, myalgia, muscular pain, nocturnal muscle cramping, weakness, and rare rhabdomyolysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>For the purpose of this narrative review, we searched for the literature suggesting the involvement of the ubiquitin\u2013proteasome system in the development of statin\u2013induced myopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Statins have been shown to up\u2013regulate the expression of the muscle\u2013specific ubiquitin\u2013proteasome system as the major non\u2013lysosomal intracellular protein degradation system. It has been postulated that statins may provoke instability in the myocyte cell membrane when subjected to eccentric exercise stress, triggering activation of intracellular proteolytic cascades and changes in protein degradation machinery. This is accompanied by the up\u2013regulation of a series of genes implicated in protein catabolism, in addition to those of the ubiquitin\u2013proteasome system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Based on the available literature, it seems that the involvement of ubiquitin\u2013proteasome system is potentially implicated in the pathophysiology of statin\u2013induced myopathy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12579","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T05:00:16Z","timestamp":1596430816000},"page":"1177-1186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Pathophysiological mechanisms of statin\u2010associated myopathies: possible role of the ubiquitin\u2010proteasome system"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8656-1444","authenticated-orcid":false,"given":"Amirhossein","family":"Sahebkar","sequence":"first","affiliation":[{"name":"Halal Research Center of IRI FDA  Tehran Iran"},{"name":"Biotechnology Research Center, Pharmaceutical Technology Institute Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Neurogenic Inflammation Research Center Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Polish Mother's Memorial Hospital Research Institute (PMMHRI)  Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arrigo F.G.","family":"Cicero","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences Alma Mater Studiorum\u2014Universit\u00e0 di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Di Giosia","sequence":"additional","affiliation":[{"name":"Department of life, health and environmental sciences San Salvatore Hospital University of L'Aquila  L'Aquila Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Pomilio","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy University of Camerino  Camerino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosimo Andrea","family":"Stamerra","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy University of Camerino  Camerino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Giorgini","sequence":"additional","affiliation":[{"name":"Department of life, health and environmental sciences San Salvatore Hospital University of L'Aquila  L'Aquila Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Ferri","sequence":"additional","affiliation":[{"name":"Department of life, health and environmental sciences San Salvatore Hospital University of L'Aquila  L'Aquila Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"von Haehling","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology University of G\u00f6ttingen Medical Center  G\u00f6ttingen Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6690-6874","authenticated-orcid":false,"given":"Maciej","family":"Banach","sequence":"additional","affiliation":[{"name":"Department of Hypertension WAM University Hospital in Lodz, Medical University of Lodz  Lodz Poland"},{"name":"Polish Mother's Memorial Hospital Research Institute (PMMHRI)  Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tannaz","family":"Jamialahmadi","sequence":"additional","affiliation":[{"name":"Biotechnology Research Center, Pharmaceutical Technology Institute Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Department of Food Science and Technology, Quchan Branch Islamic Azad University  Quchan Iran"},{"name":"Department of Nutrition, Faculty of Medicine Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1552"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010037908060"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.50.1.57"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.24.7151"},{"key":"e_1_2_8_6_1","unstructured":"HershkoA CiechanoverA.The ubiquitin system. 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