The complement system in neurodegenerative diseases

Nimmo, Jacqui, Byrne, Robert A.J., Daskoulidou, Nikoleta, Watkins, Lewis M., Carpanini, Sarah M., Zelek, Wioleta M. and Morgan, B. Paul ORCID: https://orcid.org/0000-0003-4075-7676 2024. The complement system in neurodegenerative diseases. Clinical Science 138 (6) , pp. 387-412. 10.1042/cs20230513

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Abstract

Complement is an important component of innate immune defence against pathogens and crucial for efficient immune complex disposal. These core protective activities are dependent in large part on properly regulated complement-mediated inflammation. Dysregulated complement activation, often driven by persistence of activating triggers, is a cause of pathological inflammation in numerous diseases, including neurological diseases. Increasingly, this has become apparent not only in well-recognized neuroinflammatory diseases like multiple sclerosis but also in neurodegenerative and neuropsychiatric diseases where inflammation was previously either ignored or dismissed as a secondary event. There is now a large and rapidly growing body of evidence implicating complement in neurological diseases that cannot be comprehensively addressed in a brief review. Here, we will focus on neurodegenerative diseases, including not only the ‘classical’ neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, but also two other neurological diseases where neurodegeneration is a neglected feature and complement is implicated, namely, schizophrenia, a neurodevelopmental disorder with many mechanistic features of neurodegeneration, and multiple sclerosis, a demyelinating disorder where neurodegeneration is a major cause of progressive decline. We will discuss the evidence implicating complement as a driver of pathology in these diverse diseases and address briefly the potential and pitfalls of anti-complement drug therapy for neurodegenerative diseases.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Portland Press
ISSN:	0143-5221
Funders:	MRC
Date of First Compliant Deposit:	25 March 2024
Date of Acceptance:	1 March 2024
Last Modified:	01 Jul 2024 10:30
URI:	https://orca.cardiff.ac.uk/id/eprint/167520

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