{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:06:49Z","timestamp":1790532409513,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T00:00:00Z","timestamp":1727049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32220103006"],"award-info":[{"award-number":["32220103006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271524"],"award-info":[{"award-number":["82271524"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>While the gradually aggravated motor and non\u2010motor disorders of Parkinson's disease (PD) lead to progressive disability and frequent falling, skeletal muscle impairment may contribute to this condition. The leucine\u2010rich repeat kinase2 (LRRK2) is a common disease\u2010causing gene in PD. Little is known about its role in skeletal muscle impairment and its underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate whether the mutation in LRRK2 causes skeletal muscle impairment, we used 3\u2010month\u2010old (3mo) and 14\u2010month\u2010old (14mo) LRRK2<jats:sup>G2019S<\/jats:sup> transgenic (TG) mice as a model of PD, compared with the age\u2010matched littermate wild\u2010type (WT) controls. We measured the muscle mass and strength, ultrastructure, inflammatory infiltration, mitochondrial morphology and dynamics dysfunction through behavioural analysis, electromyography (EMG), immunostaining, transmission electron microscopy (TEM) and other molecular biology techniques.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The 3mo\u2010TG mice display mild skeletal muscle impairment with spontaneous potentials in EMG (increased by 130%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), myofibre necrosis\u00a0(<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and myosin heavy chain\u2010II changes (reduced by 19%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). The inflammatory cells and macrophage infiltration are significantly increased (CD8a<jats:sup>+<\/jats:sup> and CD68<jats:sup>+<\/jats:sup> cells up 1060% and 579%, respectively, both <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) compared with the WT mice. All of the above pathogenic processes are aggravated by aging. The 14mo\u2010TG mice EMG examinations show a reduced duration (by 31%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) and increased polyphasic waves of motor unit action potentials (by 28%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). The 14mo\u2010TG mice present motor behavioural deficits (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), muscle strength and mass reduction by 37% and 8% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 and <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01, respectively). A remarkable increase in inflammatory infiltration is accompanied by pro\u2010inflammatory cytokines in the skeletal muscles. TEM analysis shows muscle fibre regeneration with the reduced length of sarcomeres (by 6%;<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). The muscle regeneration is activated as Pax7<jats:sup>+<\/jats:sup> cells increased by 106% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), andmyoblast determination protein elevated by 71% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). We also document the morphological changes and dynamics dysfunction of mitochondria with the increase of mitofusin1 by 43% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05)\u00a0and voltage\u2010dependent anion channel 1 by 115% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) in the skeletal muscles of 14mo\u2010TG mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, these findings may provide new insights into the clinical and pathogenic involvement of LRRK2<jats:sup>G2019<\/jats:sup> mutation in muscles, suggesting that the diseases may affect not only midbrain dopaminergic neurons, but also other tissues, and it may help overall clinical management of this devastating disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13604","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T09:45:10Z","timestamp":1727084710000},"page":"2595-2607","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["LRRK2<sup>G2019S<\/sup> Gene Mutation Causes Skeletal Muscle Impairment in Animal Model of Parkinson's Disease"],"prefix":"10.1002","volume":"15","author":[{"given":"Yiying","family":"Hu","sequence":"first","affiliation":[{"name":"Key Laboratory of Liaoning Province for Research on the Pathogenic Mechanisms of Neurological Diseases The First Affiliated Hospital of Dalian Medical University  Dalian China"},{"name":"Department of Neurology The First Affiliated Hospital of Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijia","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Liaoning Province for Research on the Pathogenic Mechanisms of Neurological Diseases The First Affiliated Hospital of Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunli","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Tian","sequence":"additional","affiliation":[{"name":"Key Laboratory of Liaoning Province for Research on the Pathogenic Mechanisms of Neurological Diseases The First Affiliated Hospital of Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Liaoning Province for Research on the Pathogenic Mechanisms of Neurological Diseases The First Affiliated Hospital of Dalian Medical 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