AUTHOR=Chen Jin Y. , Sanghani Nirav , Palmer Kaitlyn , Li Yuebing , Lin Feng , Abbatemarco Justin R. 

TITLE=Complement activation in immunological neurological disorders: mechanisms and therapeutic strategies

JOURNAL=Frontiers in Neurology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1695461

DOI=10.3389/fneur.2025.1695461

ISSN=1664-2295

ABSTRACT=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.