---
title: "Complement and Complement-Targeted Therapeutics in Neurological Diseases"
id: "nature-reviews-neurology-0-role-of-complement-and-complement-targeted-therapeutics-in-neurological-diseases"
canonical_url: "https://medichelpline.com/clinical-feed/nature-reviews-neurology-0-role-of-complement-and-complement-targeted-therapeutics-in-neurological-diseases"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "Nature Reviews Neurology"
source_url: "https://www.nature.com/articles/s41582-026-01261-4"
published_at: "2026-09-03T12:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Complement and Complement-Targeted Therapeutics in Neurological Diseases
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/nature-reviews-neurology-0-role-of-complement-and-complement-targeted-therapeutics-in-neurological-diseases
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** Nature Reviews Neurology
- **Source URL:** [Original Journal Publication](https://www.nature.com/articles/s41582-026-01261-4)
- **Published At:** 2026-09-03T12:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The **complement** system is a set of plasma and membrane proteins that bridge innate and adaptive humoral immunity and also contributes to brain development and nervous system homeostasis. - Dysregulated or inappropriate complement activation is implicated across many autoimmune and **neurodegenerative** neurological disorders, including conditions affecting the central nervous system (CNS), peripheral nervous system (PNS) and muscle. - Several **FDA-approved** complement-targeted agents exist, primarily for diseases driven by complement-fixing pathogenic antibodies (for example, **myasthenia gravis** and **neuromyelitis optica spectrum disorder**), and numerous additional biologic agents are in ongoing phase I–III trials. - Experimental data indicate that some complement components can have tissue-protective roles in CNS diseases such as **Alzheimer disease** and **multiple sclerosis**, supporting the need for selective modulation of pathways rather than broad complement blockade. - Emerging therapies increasingly target proximal complement components (for example, **C1**), but proximal blockade carries heightened concerns about invasive infections and disruption of physiological complement functions. - Future development requires nuanced drug design, attention to risks versus benefits, and systematic diagnostic guidance that integrates reliable, disease-specific biomarkers to enable personalized complement-targeted therapy. - The review includes schematic representations of complement pathways (Fig. 1) and the expanding range of complement therapeutics (Fig. 2), and cites foundational and recent literature on complement function, synapse pruning, neuroinflammation and therapeutic strategies. - Overall, anti-complement therapeutics are poised to reshape treatment paradigms in autoimmune neurologic conditions amid a crowded biologic landscape targeting multiple immune mechanisms.
## Clinical Analysis & Structured Key Points
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Advertisement [ ![Nature Reviews Neurology](https://media.springernature.com/full/nature-cms/uploads/product/nrneurol/header-0e3b6e66371daa4e48420b30ea763bd4.svg) ](https://www.nature.com/nrneurol) * [ View all journals ](https://www.nature.com/siteindex) * [ Saved research ](https://www.nature.com/saved-research) * [ Search ](javascript:;) ## Search Search articles by subject, keyword or author Show results from All journals This journal Search [ Advanced search ](https://www.nature.com/search/advanced) ### Quick links * [Explore articles by subject](https://www.nature.com/subjects) * [Find a job](https://www.nature.com/naturecareers) * [Guide to authors](https://www.nature.com/authors/index.html) * [Editorial policies](https://www.nature.com/authors/editorial_policies/) * [Log in](https://idp.nature.com/auth/personal/springernature?redirect_uri=https://www.nature.com/articles/s41582-026-01261-4) * [ Content Explore content ](javascript:;) ## Explore content * [ Research articles ](https://www.nature.com/nrneurol/research-articles) * [ Reviews & Analysis ](https://www.nature.com/nrneurol/reviews-and-analysis) * [ News & Comment ](https://www.nature.com/nrneurol/news-and-comment) * [ Current issue ](https://www.nature.com/nrneurol/current-issue) * [ Collections ](https://www.nature.com/nrneurol/collections) * [Follow us on Facebook ](https://www.facebook.com/NatureReviews) * [Follow us on X ](https://twitter.com/NatRevNeurol) * [ Subscribe ](https://www.nature.com/nrneurol/subscribe) * [Sign up for alerts ](https://journal-alerts.springernature.com/subscribe?journal_id=41582) * [ RSS feed ](https://www.nature.com/nrneurol.rss) * [ About the journal ](javascript:;) ## About the journal * [ Aims & Scope ](https://www.nature.com/nrneurol/aims) * [ Journal Information ](https://www.nature.com/nrneurol/journal-information) * [ Editorial policies ](https://www.nature.com/nrneurol/editorial-policies) * [ About the Editors ](https://www.nature.com/nrneurol/editors) * [ Reviews Cross-Journal Editorial Team ](https://www.nature.com/nrneurol/reviews-cross-journal-editorial-team) * [ Journal Credits ](https://www.nature.com/nrneurol/journal-credits) * [ Editorial input and checks ](https://www.nature.com/nrneurol/editorial-input-and-checks) * [ Editorial Values Statement ](https://www.nature.com/nrneurol/editorial-values-statement) * [ Journal Metrics ](https://www.nature.com/nrneurol/journal-impact) * [ Publishing model ](https://www.nature.com/nrneurol/publishing-model) * [ Web Feeds ](https://www.nature.com/nrneurol/web-feeds) * [ Contact ](https://www.nature.com/nrneurol/contact) * [ Publish with us ](javascript:;) ## Publish with us * [ For Authors ](https://www.nature.com/nrneurol/for-authors) * [ For Referees ](https://www.nature.com/nrneurol/for-referees) * [Submit manuscript ](https://mts-nrneurol.nature.com/cgi-bin/main.plex) * [ Subscribe ](https://www.nature.com/nrneurol/subscribe) * [ Sign up for alerts ](https://journal-alerts.springernature.com/subscribe?journal_id=41582) * [ RSS feed ](https://www.nature.com/nrneurol.rss) 1. [nature](https://www.nature.com/) 2. [nature reviews neurology](https://www.nature.com/nrneurol) 3. [review articles](https://www.nature.com/nrneurol/articles?type=review-article) 4. article * Review Article * Published: 03 September 2026 # Role of complement and complement-targeted therapeutics in neurological diseases * [Marinos C. Dalakas](https://www.nature.com/articles/s41582-026-01261-4#auth-Marinos_C_-Dalakas-Aff1-Aff2) [ORCID: orcid.org/0000-0001-7070-1134](https://orcid.org/0000-0001-7070-1134)[1](https://www.nature.com/articles/s41582-026-01261-4#Aff1),[2](https://www.nature.com/articles/s41582-026-01261-4#Aff2) & * [Jan D. Lünemann](https://www.nature.com/articles/s41582-026-01261-4#auth-Jan_D_-L_nemann-Aff3-Aff4)[3](https://www.nature.com/articles/s41582-026-01261-4#Aff3),[4](https://www.nature.com/articles/s41582-026-01261-4#Aff4) [_Nature Reviews Neurology_](https://www.nature.com/nrneurol) (2026) [Cite this article](https://www.nature.com/articles/s41582-026-01261-4#citeas) [ Save article ](https://www.nature.com/articles/s41582-026-01261-4/save-research?_csrf=oTBrkwST0EV9PaikPWrblvK7UmcUY7X6) [ View saved research ](https://www.nature.com/saved-research) ## Abstract Complement comprises a group of plasma and membrane proteins that provide an effective bridging function for innate and adaptive humoral immunity. Understanding complement pathophysiology is fundamental given that inappropriate complement function in host defence can lead to infectious diseases and inefficient disposal of altered, damaged or senescent cells can lead to or enhance autoimmune neurological processes. Although the rising number of approved drugs targeting complement pathways remains primarily focused on diseases with complement-fixing pathogenic antibodies (such as myasthenia gravis and neuromyelitis optica spectrum disorder), a robust pipeline of emerging treatments holds promise for expanding complement-targeted therapies to a broader spectrum of autoimmune neurological diseases, such as multiple sclerosis and even neurodegenerative diseases such as Alzheimer disease or amyotrophic lateral sclerosis. This Review presents insights into complement biology as it relates to the development or initiation of autoimmune and possibly degenerative diseases affecting the central and peripheral nervous systems or muscle. The effects, merits, risks and challenges of marketed drugs or biologic agents in ongoing phase I–III clinical trials engineered to inhibit proximal or distal components of the complement cascade are also discussed. Anti-complement therapeutics are destined to change the treatment of autoimmune neurologic conditions in which the therapeutic landscape is now becoming crowded with biologic agents targeting other key autoimmunity factors. ## Key points * Complement has a vital role in host immune defences, but also in brain development and nervous system homeostasis. * Aberrant complement activation is a prominent feature in many autoimmune and neurodegenerative neurological diseases. * Complement-targeted therapies are a rapidly growing area in neurology, with several FDA-approved agents already available and others in ongoing phase II–III clinical trials. * Experimental evidence indicates that specific complement components exert tissue-protective effects in certain CNS diseases, such as Alzheimer disease and multiple sclerosis, underscoring the need for nuanced, pathway-selective modulation of complement activity rather than broad inhibition as a therapeutic strategy. * Emerging neurological therapies target proximal complement components such as C1, but the associated risks of invasive infections and disruption of physiological complement functions must be carefully considered. * Future drug development and personalized therapeutic approaches targeting complement require systematic diagnostic guidance that leverages reliable disease-specific biomarkers. This is a preview of subscription content, [access via your institution](https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41582-026-01261-4) ## Access options [ Access through your institution ](https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41582-026-01261-4) Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription 27,99 € / 30 days cancel any time [Learn more](https://shop.nature.com/products/plus/?region=ROW) Subscribe to this journal Receive 12 print issues and online access 176,64 € per year only 14,72 € per issue [Learn more](https://www.nature.com/nrneurol/subscribe) Buy this article * Purchase on SpringerLink * Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout ### Additional access options: * [Log in](https://idp.nature.com/authorize/natureuser?client_id=grover&redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41582-026-01261-4) * [Learn about institutional subscriptions](https://www.springernature.com/gp/librarians/licensing/license-options) * [Read our FAQs](https://support.nature.com/en/support/home) * [Contact customer support](https://www.springernature.com/gp/contact) **Fig. 1: Complement pathways.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41582-026-01261-4/MediaObjects/41582_2026_1261_Fig1_HTML.png) **Fig. 2: The expanding spectrum of complement therapeutics.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41582-026-01261-4/MediaObjects/41582_2026_1261_Fig2_HTML.png) ### Explore related subjects Discover the latest articles and news in related subjects. * [Neurological disorders](https://www.nature.com/subjects/neurological-disorders) * [Therapeutics](https://www.nature.com/subjects/therapeutics) ## References 1. 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