Nature reviews. NeurologySep 4, 2026

The role of the complement immune system and related treatments in brain diseases

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 5, 2026

Abstract

A robust pipeline of emerging treatments targeting complement pathways could expand therapies for autoimmune neurological diseases.

Complement proteins play a crucial role in both innate and adaptive immunity.
Inappropriate functioning of the complement system may contribute to infectious diseases and autoimmune neurological processes.
Current approved drugs mainly target diseases with complement-fixing pathogenic antibodies, like myasthenia gravis.
There is potential for new therapies to address a wider range of autoimmune neurological conditions, including multiple sclerosis and neurodegenerative diseases.
The review discusses the effects and challenges of existing and emerging anti-complement therapeutics in clinical trials.

Simplified

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.

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The role of the complement immune system and related treatments in brain diseases

Abstract

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