REVIEW article
Front. Neurol.
Sec. Multiple Sclerosis and Neuroimmunology
Complement Activation in Immunological Neurological Disorders: Mechanisms and Therapeutic Strategies
Provisionally accepted
- 1Cleveland Clinic, Cleveland, United States
- 2University of Connecticut, Storrs, United States
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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.
Keywords: complement, innate immunity, Myasthenia Gravis, aquaporin-4 IgG-positiveneuromyelitis optica spectrum disorder, complement-targeted therapies
Received: 29 Aug 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Chen, Sanghani, Palmer, Li, Lin and Abbatemarco. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Justin R. Abbatemarco, justinabbatemarco@gmail.com
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