{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:09:27Z","timestamp":1792638567832,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,11,10]],"date-time":"2024-11-10T00:00:00Z","timestamp":1731196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Charcot\u2013Marie\u2013Tooth (CMT) type 1 neuropathies are the most common inherited diseases of the peripheral nervous system. Although more than 100 causative genes have been identified so far, therapeutic options are still missing. We could previously identify that early\u2010onset physical exercise (voluntary wheel running, VWR) dampens peripheral nerve inflammation, improves neuropathological alterations, and clinical outcome in Cx32def mice, a model for CMT1X. We here investigate the clinical and histopathological effect of late\u2010onset exercise in Cx32def mice at an advanced disease stage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Nine\u2010month\u2010old Cx32def mice were allowed to run for 4\u2009days\/week on a commercially available running wheel for 3\u2009months, with timely limited access to running wheels, representing a running distance of ~2000\u2009m. Control mutants had no access to running wheels. Afterward, mice were investigated by distinct functional tests and by immunohistochemical and electron microscopical techniques.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that late\u2010onset physical exercise (late VWR<jats:sup>lim<\/jats:sup>) prevented the robust functional decline in 12\u2010month\u2010old Cx32def mice. This was accompanied by improved neuromuscular innervation of distal muscles and axonal preservation in femoral quadriceps nerves. In contrast to a \u201cpre\u2010symptomatic\u201d start of physical exercise in Cx32def mice, late\u2010onset VWR did not alter nerve inflammation and myelin thickness at 12\u2009months of age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We conclude that VWR has robust beneficial effects on nerve function in Cx32def mice, even when applied at a progressed disease stage. These results have important translational implications, suggesting that physical exercise might be an effective treatment option for CMT1 patients, even when disease symptoms have already progressed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jns.12669","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T01:48:39Z","timestamp":1731289719000},"page":"494-504","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Physical exercise halts further functional decline in an animal model for Charcot\u2013Marie\u2013Tooth disease <scp>1X<\/scp> at an advanced disease stage"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0476-445X","authenticated-orcid":false,"given":"Dennis","family":"Klein","sequence":"first","affiliation":[{"name":"Department of Neurology, Developmental Neurobiology University Hospital W\u00fcrzburg  W\u00fcrzburg 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