{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:31:39Z","timestamp":1774877499031,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India","award":["71\/2-Edu-16\/5573-75"],"award-info":[{"award-number":["71\/2-Edu-16\/5573-75"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Background: Muscle atrophy is a major feature of Limb Girdle Muscular Dystrophy R1 (LGMDR1) patients, but its underlying molecular mechanisms have not been fully explored. While the ubiquitin\u2013proteasome system (UPS) is known to be involved in muscle protein degradation, inflammation commonly observed in LGMDR1 patients may further activate the UPS. This study aimed to explore the role of inflammation in the muscle atrophy of LGMDR1 patients. Methods: Muscle biopsies from six confirmed LGMDR1 patients (with CAPN3 variants and reduced calpain-3 protein expression) were analyzed for atrophy-related markers, MuRF1 and Atrogin-1, using qRT-PCR and Western blotting. The expression of cytokines, TNF-\u03b1, IL-1\u03b2, and IL-6 was analyzed by qRT-PCR from muscle biopsies and by ELISA from serum samples. The NF\u03baB, FOXO1, and FOXO3 gene expression was analyzed using qRT-PCR and Western blotting from muscle biopsies. Results: Elevated TNF-\u03b1 levels were associated with increased UPS activity, reflected by upregulated NF\u03baB, FOXO1, MuRF1, and Atrogin-1 expression in LGMDR1. Conclusion: Our findings indicate that increased TNF-\u03b1 expression is associated with muscle wasting in LGMDR1 patients by targeting UPS pathway mediators that activate ubiquitin ligases\u2014MuRF1 and Atrogin-1. These findings suggest that targeting TNF-\u03b1 signaling and its downstream factors may help develop therapeutic interventions to prevent muscle atrophy in LGMDR1 patients.<\/jats:p>","DOI":"10.3390\/cimb48040361","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T12:11:44Z","timestamp":1774872704000},"page":"361","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammation-Linked Muscle Atrophy in Limb Girdle Muscular Dystrophy R1 (LGMDR1): Insights into Disease Mechanisms"],"prefix":"10.3390","volume":"48","author":[{"given":"Sukanya","family":"Banerjee","sequence":"first","affiliation":[{"name":"Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bishan Dass","family":"Radotra","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manni","family":"Luthra-Guptasarma","sequence":"additional","affiliation":[{"name":"Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manoj K.","family":"Goyal","sequence":"additional","affiliation":[{"name":"Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0092-8674(95)90368-2","article-title":"Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A","volume":"81","author":"Richard","year":"1995","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"463","DOI":"10.3346\/jkms.2007.22.3.463","article-title":"Mutations of CAPN3 in Korean patients with limb-girdle muscular dystrophy","volume":"22","author":"Shin","year":"2007","journal-title":"J. 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