{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T11:30:18Z","timestamp":1768735818793,"version":"3.49.0"},"reference-count":47,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Association Fran\u00e7oise contre les Myopathies","award":["#18620"],"award-info":[{"award-number":["#18620"]}]},{"name":"Association Fran\u00e7oise contre les Myopathies","award":["#23000"],"award-info":[{"award-number":["#23000"]}]},{"name":"Association Fran\u00e7oise contre les Myopathies","award":["#28892"],"award-info":[{"award-number":["#28892"]}]},{"name":"Association Fran\u00e7oise contre les Myopathies","award":["GGP15140"],"award-info":[{"award-number":["GGP15140"]}]},{"name":"Association Fran\u00e7oise contre les Myopathies","award":["GGP20097"],"award-info":[{"award-number":["GGP20097"]}]},{"name":"Association Fran\u00e7oise contre les Myopathies","award":["#MDA 577888"],"award-info":[{"award-number":["#MDA 577888"]}]},{"name":"Italian Telethon Foundation","award":["#18620"],"award-info":[{"award-number":["#18620"]}]},{"name":"Italian Telethon Foundation","award":["#23000"],"award-info":[{"award-number":["#23000"]}]},{"name":"Italian Telethon Foundation","award":["#28892"],"award-info":[{"award-number":["#28892"]}]},{"name":"Italian Telethon Foundation","award":["GGP15140"],"award-info":[{"award-number":["GGP15140"]}]},{"name":"Italian Telethon Foundation","award":["GGP20097"],"award-info":[{"award-number":["GGP20097"]}]},{"name":"Italian Telethon Foundation","award":["#MDA 577888"],"award-info":[{"award-number":["#MDA 577888"]}]},{"name":"Muscular Dystrophy Association","award":["#18620"],"award-info":[{"award-number":["#18620"]}]},{"name":"Muscular Dystrophy Association","award":["#23000"],"award-info":[{"award-number":["#23000"]}]},{"name":"Muscular Dystrophy Association","award":["#28892"],"award-info":[{"award-number":["#28892"]}]},{"name":"Muscular Dystrophy Association","award":["GGP15140"],"award-info":[{"award-number":["GGP15140"]}]},{"name":"Muscular Dystrophy Association","award":["GGP20097"],"award-info":[{"award-number":["GGP20097"]}]},{"name":"Muscular Dystrophy Association","award":["#MDA 577888"],"award-info":[{"award-number":["#MDA 577888"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Limb\u2013girdle muscular dystrophy type 2E\/R4 (LGMD2E\/R4) is a rare disease that currently has no cure. It is caused by defects in the SGCB gene, mainly missense mutations, which cause the impairment of the sarcoglycan complex, membrane fragility, and progressive muscle degeneration. Here, we studied the fate of some \u03b2-sarcoglycan (\u03b2-SG) missense mutants, confirming that, like \u03b1-SG missense mutants, they are targeted for degradation through the ubiquitin\u2013proteasome system. These data, collected using HEK-293 cells expressing either the I119F- or Y184C mutants of \u03b2-SG, were subsequently confirmed in primary myotubes derived from an LGMD2E\/R4 patient carrying a homozygous I92T mutation. The knowledge that \u03b2-SG with an amino acid substitution shares a pathway of degradation with \u03b1-SG mutants, allowed us to explore the pharmacological approach successfully tested in LGMD2D\/R3. Several CFTR correctors, particularly corrector C17, preserved \u03b2-SG mutants from degradation and promoted localization at the sarcolemma of the entire SG complex. The presence of the complex, despite containing a mutated subunit, improved sarcolemma integrity, as evidenced by the reduced creatine kinase release from myotubes under hypoosmotic stress. These results suggest that \u03b2-SG missense mutants undergo proteasomal degradation as \u03b1-SG mutants, and that CFTR correctors, particularly C17, may be used as a potential therapeutic option for recovering and stabilizing the SG complex in patients with sarcoglycanopathies.<\/jats:p>","DOI":"10.3390\/ijms252413313","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T03:52:49Z","timestamp":1733975569000},"page":"13313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Efficacy of Cystic Fibrosis Transmembrane Regulator Corrector C17 in Beta-Sarcoglycanopathy\u2014Assessment of Patient\u2019s Primary Myotubes"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8761-1730","authenticated-orcid":false,"given":"Martina","family":"Scano","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, Via U. Bassi 58\/B, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1848-0677","authenticated-orcid":false,"given":"Alberto","family":"Benetollo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, Via U. Bassi 58\/B, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3277-4242","authenticated-orcid":false,"given":"Francesco","family":"Dalla Barba","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, Via U. Bassi 58\/B, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7054-5116","authenticated-orcid":false,"given":"Eylem Emek","family":"Akyurek","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedicine and Food Science, University of Padova, Agripolis, Legnaro, 35020 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7742-339X","authenticated-orcid":false,"given":"Marcello","family":"Carotti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, Via U. Bassi 58\/B, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8884-8302","authenticated-orcid":false,"given":"Roberta","family":"Sacchetto","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedicine and Food Science, University of Padova, Agripolis, Legnaro, 35020 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9908-2442","authenticated-orcid":false,"given":"Dorianna","family":"Sandon\u00e0","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, Via U. Bassi 58\/B, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.nmd.2021.07.014","article-title":"Sarcoglycanopathies: An update","volume":"31","author":"Vainzof","year":"2021","journal-title":"Neuromuscul. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1212\/WNL.0000000000001519","article-title":"Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E","volume":"84","author":"Semplicini","year":"2015","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1080\/21678707.2020.1865916","article-title":"Assessing diagnosis and managing respiratory and cardiac complications of sarcoglycanopathy","volume":"8","author":"Angelini","year":"2021","journal-title":"Expert Opin. 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