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The role of an impaired proteostasis as the underlying causal mechanism of muscle atrophy is a well\u2010established concept. From the earliest work on muscle atrophy and the identification of the first atrogenes, the hyper\u2010activation of the proteolytic systems, such as autophagy and the ubiquitin proteasome system, has been recognized as the major driver of atrophy. However, the role of other key regulators of proteostasis, the chaperone proteins, has been largely overlooked. Chaperone proteins play a pivotal role in protein folding and in preventing the aggregation of misfolded proteins. Indeed, some chaperones, such as \u03b1B\u2010crystallin and Hsp25, are involved in compensatory responses aimed at counteracting protein aggregation during sarcopenia. Chaperones also regulate different intracellular signalling pathways crucial for atrogene expression and the control of protein catabolism, such as the AKT and NF\u2010kB pathways, which are regulated by Hsp70 and Hsp90. Furthermore, the downregulation of certain chaperones causes severe muscle wasting per se and experimental strategies aimed at preventing this downregulation have shown promising results in mitigating or reversing muscle atrophy. This highlights the therapeutic potential of targeting chaperones and confirms their crucial anti\u2010atrophic functions. In this review, we summarize the most relevant data showing the modulation and the causative role of chaperone proteins in different types of skeletal muscle atrophies.<\/jats:p>","DOI":"10.1002\/jcsm.13659","type":"journal-article","created":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T01:40:49Z","timestamp":1734745249000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Chaperone Proteins: The Rising Players in Muscle Atrophy"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8978-9308","authenticated-orcid":false,"given":"Davide","family":"Acquarone","sequence":"first","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences University of Turin  Turin 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