{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:05:31Z","timestamp":1784091931469,"version":"3.55.0"},"reference-count":115,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>ICU-acquired weakness (ICUAW) is a clinical condition characterized by muscle weakness in critically ill patients that is not directly attributable to the underlying illness. It affects approximately 40% of intensive care unit patients, primarily impairing the limbs and respiratory muscles, and can compromise motor and respiratory function even after recovery from acute illness. ICUAW exhibits heterogeneous phenotypes. In addition, diverse risk factors influence its occurrence. Although this condition is recognized, the underlying mechanisms contributing to critical illness-associated muscle dysfunction remain poorly understood and are likely interrelated. This review summarizes the current experimental evidence from translational studies involving diverse muscle biopsies under various conditions, providing insights into normal skeletal muscle physiology and its alterations in critical illness-associated muscle dysfunction. Here, we focus on muscle ultrastructure, mitochondrial function, atrophy, protein breakdown, inflammation, and key molecular pathways, with consideration of the proposed role of NLRP3 inflammasome signalling, for which direct experimental evidence in human skeletal muscle during critical illness remains limited and constitutes a priority area for future mechanistic research.<\/jats:p>","DOI":"10.3390\/ijms27146114","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:27:31Z","timestamp":1783531651000},"page":"6114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Muscle Dysfunction in Critical Illness: Established Mechanisms and the Potential Contribution of the NLRP3 Inflammasome"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5596-1800","authenticated-orcid":false,"given":"\u00d3scar","family":"Arellano-P\u00e9rez","sequence":"first","affiliation":[{"name":"PhD Program in Biomedical Sciences, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380453, Chile"},{"name":"Public Assistance Emergency Hospital, Santiago 8320000, Chile"},{"name":"Adult Patients Critical Centre, INDISA Clinic, Santiago 7510506, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joceline","family":"Arias-D\u00edaz","sequence":"additional","affiliation":[{"name":"Adult Patients Critical Centre, INDISA Clinic, Santiago 7510506, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0098-7791","authenticated-orcid":false,"given":"Enzo","family":"Jim\u00e9nez-Oliva","sequence":"additional","affiliation":[{"name":"Institute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, Santiago 8380544, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7625-7978","authenticated-orcid":false,"given":"Denisse","family":"Valladares-Ide","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, University of O\u2019Higgins, Rancagua 2820000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5068-7259","authenticated-orcid":false,"given":"Lilian","family":"Jara","sequence":"additional","affiliation":[{"name":"Human Genetics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1383-7961","authenticated-orcid":false,"given":"Paola","family":"Llanos","sequence":"additional","affiliation":[{"name":"Institute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, Santiago 8380544, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1097\/WNP.0000000000000658","article-title":"Critical Illness Myopathy","volume":"37","author":"Tankisi","year":"2020","journal-title":"J. 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