{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:44:01Z","timestamp":1783446241603,"version":"3.55.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Transgenic Core Facility","award":["AS-CFII-108-104"],"award-info":[{"award-number":["AS-CFII-108-104"]}]},{"name":"Transgenic Core Facility","award":["AS-IA-106-L04"],"award-info":[{"award-number":["AS-IA-106-L04"]}]},{"name":"Transgenic Core Facility","award":["AS-IA-111-L01"],"award-info":[{"award-number":["AS-IA-111-L01"]}]},{"name":"Animal Facility of the Institute of Molecular Biology, Academia Sinica"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Many genes with distinct molecular functions have been linked to genetically heterogeneous amyotrophic lateral sclerosis (ALS), including SuperOxide Dismutase 1 (SOD1) and Valosin-Containing Protein (VCP). SOD1 converts superoxide to oxygen and hydrogen peroxide. VCP acts as a chaperon to regulate protein degradation and synthesis and various other cellular responses. Although the functions of these two genes differ, in the current report we show that overexpression of wild-type VCP in mice enhances lifespan and maintains the size of neuromuscular junctions (NMJs) of both male and female SOD1G93A mice, a well-known ALS mouse model. Although VCP exerts multiple functions, its regulation of ER formation and consequent protein synthesis has been shown to play the most important role in controlling dendritic spine formation and social and memory behaviors. Given that SOD1 mutation results in protein accumulation and aggregation, it may direct VCP to the protein degradation pathway, thereby impairing protein synthesis. Since we previously showed that the protein synthesis defects caused by Vcp deficiency can be improved by leucine supplementation, to confirm the role of the VCP-protein synthesis pathway in SOD1-linked ALS, we applied leucine supplementation to SOD1G93A mice and, similar to Vcp overexpression, we found that it extends SOD1G93A mouse lifespan. In addition, the phenotypes of reduced muscle strength and fewer NMJs of SOD1G93A mice are also improved by leucine supplementation. These results support the existence of crosstalk between SOD1 and VCP and suggest a critical role for protein synthesis in ASL. Our study also implies a potential therapeutic treatment for ALS.<\/jats:p>","DOI":"10.1093\/hmg\/ddae022","type":"journal-article","created":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:10:34Z","timestamp":1708560634000},"page":"935-944","source":"Crossref","is-referenced-by-count":5,"title":["<i>Vcp<\/i> overexpression and leucine supplementation extend lifespan and ameliorate neuromuscular junction phenotypes of a SOD1G93A-ALS mouse model"],"prefix":"10.1093","volume":"33","author":[{"given":"Tzyy-Nan","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology, Academia Sinica , 128 Sec 2, Academia Rd, Taipei, 11529 , Taiwan, ROC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Tzu","family":"Shih","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, Academia Sinica , 128 Sec 2, Academia Rd, Taipei, 11529 , Taiwan, ROC"},{"name":"Center for Regenerative Medicine, Massachusetts General Hospital , 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