{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T10:50:59Z","timestamp":1789296659248,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["20231121165903001"],"award-info":[{"award-number":["20231121165903001"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["C2301009"],"award-info":[{"award-number":["C2301009"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["2022SHIBS0003"],"award-info":[{"award-number":["2022SHIBS0003"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Medical Research Fund","award":["20231121165903001"],"award-info":[{"award-number":["20231121165903001"]}]},{"name":"Shenzhen Medical Research Fund","award":["C2301009"],"award-info":[{"award-number":["C2301009"]}]},{"name":"Shenzhen Medical Research Fund","award":["2022SHIBS0003"],"award-info":[{"award-number":["2022SHIBS0003"]}]},{"name":"Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions","award":["20231121165903001"],"award-info":[{"award-number":["20231121165903001"]}]},{"name":"Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions","award":["C2301009"],"award-info":[{"award-number":["C2301009"]}]},{"name":"Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions","award":["2022SHIBS0003"],"award-info":[{"award-number":["2022SHIBS0003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple sclerosis (MS) is a chronic autoimmune disease characterized by sustained neuroinflammation and demyelination within the central nervous system (CNS). Vesatolimod (VES), a selective Toll-like receptor 7 (TLR7) agonist, has demonstrated both antiviral and immunomodulatory properties; however, its potential therapeutic value in neuroinflammatory contexts remains poorly understood. In this study, we evaluated the efficacy of VES in the experimental autoimmune encephalomyelitis (EAE) model of MS and elucidated its mechanisms of action. EAE was induced in mice by immunization with myelin oligodendrocyte glycoprotein (MOG35\u201355). The therapeutic effects of VES were assessed through clinical scoring, body weight monitoring, histopathology, flow cytometry, quantitative proteomics, and Western blot analysis. Additionally, an in vitro model of lipopolysaccharide (LPS)-induced microglial activation was employed to investigate cell-autonomous mechanisms. Results showed that VES administration significantly ameliorated disease severity, reduced weight loss, and enhanced neurological function in EAE mice. Treatment with VES inhibited the differentiation of pro-inflammatory Th1 and Th17 cells while expanding regulatory T cell (Treg) populations. It also preserved blood\u2013brain barrier (BBB) integrity, attenuated demyelination, and modulated microglial activation phenotypes within the CNS. At the molecular level, VES activated the Nrf2\/HO-1 antioxidant pathway, thereby enhancing the expression of cytoprotective proteins. Proteomic profiling further revealed the downregulation of inflammation-related proteins, specifically those associated with TNF, IL-17, and NOD-like receptor signaling pathways. Collectively, these findings demonstrate that VES alleviates neuroinflammation in EAE through multimodal mechanisms\u2014including peripheral and central immune regulation, BBB protection, and activation of endogenous antioxidant defenses\u2014supporting its further development as a promising therapeutic candidate for MS.<\/jats:p>","DOI":"10.3390\/ijms26199297","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T15:54:54Z","timestamp":1758642894000},"page":"9297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neuroprotective Effects of Vesatolimod in EAE: Modulating Immune Balance and Microglial Polarization"],"prefix":"10.3390","volume":"26","author":[{"given":"Xueyu","family":"Chen","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhua","family":"Mu","sequence":"additional","affiliation":[{"name":"School of Psychology, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1056\/NEJMra1401483","article-title":"Multiple Sclerosis","volume":"378","author":"Reich","year":"2018","journal-title":"N. 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