{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:17:31Z","timestamp":1792034251196,"version":"4.4.0"},"reference-count":245,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Recent advances in the understanding of immune-mediated neurological disorders have led to a paradigm shift toward pathophysiology-directed therapies. Central to this progress is a deeper appreciation of the complement system, a key component of innate immunity, and its role in neuroinflammation. Complement activation, while essential for host defense and tissue homeostasis, has been implicated increasingly in a spectrum of central and peripheral neurological disorders where complement dysregulation contributes to inflammation, cellular damage, and disease progression. Breakthroughs in conditions such as myasthenia gravis and aquaporin-4 IgG-positive neuromyelitis optica spectrum disorder underscore the therapeutic potential of targeting complement pathways to improve patient outcomes. In this review, we provide a comprehensive overview of complement activation pathways, regulatory controls, and their involvement in various autoimmune neurological diseases. We also highlight current and emerging complement-targeted therapies, many of which are now completing or entering clinical trials. Together, these insights offer a holistic perspective on the complement system as both a contributor to and a target for intervention in neurological diseases.<\/jats:p>","DOI":"10.3389\/fneur.2025.1695461","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T05:14:21Z","timestamp":1764652461000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Complement activation in immunological neurological disorders: mechanisms and therapeutic strategies"],"prefix":"10.3389","volume":"16","author":[{"given":"Jin Y.","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirav","family":"Sanghani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuebing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin R.","family":"Abbatemarco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"262","DOI":"10.3389\/fimmu.2015.00262","article-title":"Complement system part I\u2013molecular mechanisms of activation and regulation","volume":"6","author":"Merle","year":"2015","journal-title":"Front Immunol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"257","DOI":"10.3389\/fimmu.2015.00257","article-title":"Complement system part ii: role in immunity","volume":"6","author":"Merle","year":"2015","journal-title":"Front Immunol"},{"key":"ref3","first-page":"21","article-title":"Serum complement after Orthotopic transplantation of the human liver","volume":"12","author":"Torisu","year":"1972","journal-title":"Clin Exp Immunol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1126\/science.163.3864.286","article-title":"Human C\u2032 3: evidence for the liver as the primary site of synthesis","volume":"163","author":"Alper","year":"1969","journal-title":"Science"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1172\/JCI110687","article-title":"Complement biosynthesis by the human hepatoma-derived cell line Hepg2","volume":"70","author":"Morris","year":"1982","journal-title":"J Clin Invest"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1084\/jem.151.3.501","article-title":"Biosynthesis of the complement components and the regulatory proteins of the alternative complement pathway by human peripheral blood monocytes","volume":"151","author":"Whaley","year":"1980","journal-title":"J Exp Med"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1042\/bj1670647","article-title":"Biosynthesis of the first component of complement by human fibroblasts","volume":"167","author":"Reid","year":"1977","journal-title":"Biochem J"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/0161-5890(93)90262-A","article-title":"Regulation of synthesis of complement protein C4 in human fibroblasts: cell-and gene-specific effects of cytokines and lipopolysaccharide","volume":"82","author":"Kulics","year":"1994","journal-title":"Immunology"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1172\/JCI113472","article-title":"Pulmonary alveolar type ii epithelial cells synthesize and secrete proteins of the classical and alternative complement pathways","volume":"81","author":"Strunk","year":"1988","journal-title":"J Clin Invest"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"4726","DOI":"10.4049\/jimmunol.154.9.4726","article-title":"Complement expression in human brain. 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