The role of complement in neurological and neuropsychiatric diseases

Abstract

The complement system is a major component of innate immunity and a potent driver of inflammation. It has key roles in host defense against pathogens but can also contribute to pathology by driving inflammation and cell damage in diverse diseases. Complement has emerged as an important factor in the pathogenesis of numerous diseases of the CNS and PNS, including infectious, autoimmune and degenerative disorders, and is increasingly implicated in neuropsychiatric disease. Establishing the roles and relevance of complement in disease pathogenesis has become ever more important in recent years as new drugs targeting the complement system have reached the clinic, and the potential for using complement analytes as disease biomarkers has been recognized. In this brief review, the author summarizes the evidence implicating complement in these diseases and outlines ways in which this new understanding can be used to aid diagnosis and improve outcome.

Keywords:

• complement
• demyelination
• inflammation
• neurodegeneration
• neuropsychiatry

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Multi-source evidence implicates complement activation as a driver of pathology in inflammatory, degenerative, infectious and traumatic brain disease.

• Complement and inflammation likely also play roles in psychiatric diseases.

• Complement dysregulation and the complotype may be risk factors for neurological and neuropsychiatric diseases.

• Anti-complement drugs already in the clinic and in development offer the prospect of novel approaches to therapy in these diseases.

Notes