{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T02:15:38Z","timestamp":1779243338727,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. Syncytin\u20101 (Syn), an envelope glycoprotein encoded by the env gene of the human endogenous retrovirus\u2010W family, has been resorted to be highly expressed in biopsies from the muscles from ALS patients; however, the specific regulatory role of Syn during ALS progression remains uncovered.<\/jats:p><jats:p>In this study, C57BL\/6 mice were injected with adeno\u2010associated virus\u2010overexpressing Syn, with or without Fasudil administration. The Syn expression was assessed by\u00a0quantitative real\u2010time polymerase chain reaction and immunohistochemistry analysis. The histological change of anterior tibial muscles was determined by hematoxylin\u2010eosin staining. Qualitative ultrastructural analysis of electron micrographs obtained from lumbar spinal cords was carried out. Serum inflammatory cytokines were assessed by enzyme linked immunosorbent assay (ELISA) assay and motor function was recorded using Basso, Beattie, and Bresnahan (BBB) scoring, climbing test and treadmill running test. Immunofluorescence and western blot assays were conducted to examine microglial\u2010 and motor neurons\u2010related proteins.<\/jats:p><jats:p>Syn overexpression significantly caused systemic inflammatory response, muscle tissue lesions, and motor dysfunction in mice. Meanwhile, Syn overexpression promoted the impairment of motor neuron, evidenced by the damaged structure of the neurons and reduced expression of microtubule\u2010associated protein 2, HB9, neuronal nuclei and neuron\u2010specific enolase in Syn\u2010induced mice. In addition, Syn overexpression greatly promoted the expression of CD16\/CD32 and inducible nitric oxide synthase\u00a0(M1 phenotype markers), and reduced the expression of CD206 and arginase 1 (M2 phenotype markers). Importantly, the above changes caused by Syn overexpression were partly abolished by Fasudil administration.<\/jats:p><jats:p>This study provides evidence that Syn\u2010activated microglia plays a pivotal role during the progression of ALS.<\/jats:p>","DOI":"10.1002\/ddr.22254","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T06:44:21Z","timestamp":1725518661000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Fasudil attenuates syncytin\u20101\u2010mediated activation of microglia and impairments of motor neurons and motor function in mice"],"prefix":"10.1002","volume":"85","author":[{"given":"Mei","family":"Mao","sequence":"first","affiliation":[{"name":"Department of Neurology Guizhou Provincial People's Hospital Guiyang Guizhou 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