{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:33:45Z","timestamp":1790483625242,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015956","name":"Special Project for Research and Development in Key areas of Guangdong Province","doi-asserted-by":"publisher","award":["2018B030337001"],"award-info":[{"award-number":["2018B030337001"]}],"id":[{"id":"10.13039\/501100015956","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019669","name":"Universidad San Jorge","doi-asserted-by":"publisher","award":["82101657"],"award-info":[{"award-number":["82101657"]}],"id":[{"id":"10.13039\/100019669","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016085","name":"Advanced Innovation Center for Human Brain Protection, Capital Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016085","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":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sarcopenia is common in patients with Parkinson's disease (PD), showing mitochondrial oxidative stress in skeletal muscle. The aggregation of \u03b1\u2010synuclein (\u03b1\u2010Syn) to induce oxidative stress is a key pathogenic process of PD; nevertheless, we know little about its potential role in regulating peripheral nerves and the function of the muscles they innervate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate the role of \u03b1\u2010Syn aggregation on neuromuscular system, we used the Thy1 promoter to overexpress human \u03b1\u2010Syn transgenic mice (mThy1\u2010hSNCA). h\u03b1\u2010Syn expression was evaluated by western blot, and its localization was determined by confocal microscopy. The impact of \u03b1\u2010Syn aggregation on the structure and function of skeletal muscle mitochondria and neuromuscular junctions (NMJs), as well as muscle mass and function were characterized by flow cytometry, transmission electron microscopy, Seahorse XF24 metabolic assay, and AAV9 in vivo injection. We assessed the regenerative effect of mitochondrial\u2010targeted superoxide dismutase (Mito\u2010TEMPO) after skeletal muscle injury in mThy1\u2010hSNCA mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overexpressed h\u03b1\u2010Syn protein localized in motor neuron axons and NMJs in muscle and formed aggregates. \u03b1\u2010Syn aggregation increased the number of abnormal mitochondrial in the intramuscular axons and NMJs by over 60% (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01), which inhibited the release of acetylcholine (ACh) from presynaptic vesicles in NMJs (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). The expression of genes associated with NMJ activity, neurotransmission and regulation of reactive oxygen species (ROS) metabolic process were significantly decreased in mThy1\u2010hSNCA mice, resulting in ROS production elevated by ~220% (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05), thereby exacerbating oxidative stress. Such process altered mitochondrial spatial relationships to sarcomeric structures, decreased Z\u2010line spacing by 36% (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) and increased myofibre apoptosis by ~10% (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). Overexpression of \u03b1\u2010Syn altered the metabolic profile of muscle satellite cells (MuSCs), including basal respiratory capacity (~170% reduction) and glycolytic capacity (~150% reduction) (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) and decreased cell migration and fusion during muscle regeneration (~60% and ~40%, respectively) (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). We demonstrated that Mito\u2010TEMPO treatment could restore the oxidative stress status (the complex I\/V protein and enzyme activities increased ~200% and ~150%, respectively), which caused by \u03b1\u2010Syn aggregation, and improve the ability of muscle regeneration after injury. In addition, the NMJ receptor fragmentation and ACh secretion were also improved.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results reveal that the \u03b1\u2010synuclein aggregation plays an important role in regulating acetylcholine release from neuromuscular junctions and induces intramuscular mitochondrial oxidative stress, which can provide new insights into the aetiology of muscle atrophy in patients with Parkinson's disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13123","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T06:14:47Z","timestamp":1669184087000},"page":"226-242","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["\u03b1\u2010Synuclein aggregation causes muscle atrophy through neuromuscular junction degeneration"],"prefix":"10.1002","volume":"14","author":[{"given":"Qiumei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurology, Geriatrics and Neurobiology, National Clinical Research Center of Geriatric Disorders, Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"Advanced Innovation Center for Human Brain Protection Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Geriatrics and Neurobiology, National Clinical Research Center of Geriatric Disorders, Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunsong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Geriatrics and Neurobiology, National Clinical Research Center of Geriatric Disorders, Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimin","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Geriatrics and Neurobiology, National Clinical Research Center of Geriatric Disorders, Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Geriatrics and Neurobiology, National Clinical Research Center of Geriatric Disorders, Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"Advanced Innovation Center for Human Brain Protection Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piu","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Geriatrics and Neurobiology, National Clinical Research Center of Geriatric Disorders, Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"Advanced Innovation Center for Human Brain Protection Capital Medical University  Beijing China"},{"name":"Clinical Center for Parkinson's Disease, Capital Medical University Beijing Institute of Geriatrics  Beijing China"},{"name":"Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"523","article-title":"Sarcopenia in Parkinson disease: Comparison of different criteria and association with disease severity","volume":"19","author":"Vetrano 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