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Complement components of the innate immune system in health and disease in the CNS
P Gasque1, Y D Dean, E P McGreal
1Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, UK. gasque@cardiff.ac.uk
Insights
The complement system in the brain can harm neurons but also aid in repair. Understanding its dual role is crucial for treating neurodegenerative diseases.
Area of Science:
- Neuroimmunology
- Complement System Biology
- Neurodegenerative Diseases
Background:
- The complement system is vital for host defense but can cause tissue damage when dysregulated.
- Complement activation is implicated in the progression of neurodegenerative disorders.
- Brain cells possess components of the complement system, including synthesis capabilities and regulatory proteins.
Purpose of the Study:
- To review evidence of the complement system's role in neurodegenerative diseases.
- To explore mechanisms of antibody-independent complement activation in conditions like Alzheimer's disease.
- To discuss the dual pro- and anti-inflammatory functions of complement fragments in the central nervous system (CNS).
Main Methods:
- Review of existing literature and evidence on complement system components and functions in brain cells.
- Summary of mechanisms for antibody-independent classical pathway activation in specific neurodegenerative diseases.
- Analysis of studies investigating complement's role in neuronal lysis, inflammation, and tissue repair.
Main Results:
- Brain cells synthesize a complete complement system, including inhibitors and receptors.
- Antibody-independent classical complement pathway activation occurs in Alzheimer's, Huntington's, and Pick's diseases.
- Complement activation can lead to neuronal lysis but also exhibits pro- and anti-inflammatory effects, and contributes to CNS repair.
Conclusions:
- The complement system is actively involved in the CNS, influencing neuroinflammation and neurodegeneration.
- Complement activation in neurodegenerative diseases has complex consequences, including potential therapeutic targets.
- Further research into complement's multifaceted role is needed for effective treatment strategies in CNS disorders.
Abstract:
The innate immune system and notably the complement (C) system play important roles in host defense to recognise and kill deleterious invaders or toxic entities, but activation at inappropriate sites or to an excessive degree can cause severe tissue damage. C has been implicated as a factor in the exacerbation and propagation of tissue injury in numerous diseases including neurodegenerative disorders. In this article, we review the evidence indicating that brain cells can synthesise a full lytic C system and also express specific C inhibitors (to protect from C activation and C lysis) and C receptors (involved in cell activation, chemotaxis and phagocytosis). We also summarise the mechanisms involved in the antibody-independent activation of the classical pathway of C in Alzheimer's disease, Huntington's disease and Pick's disease. Although the primary role of C activation on a target cell is to induce cell lysis (particularly of neurons), we present evidence indicating that C (C3a, C5a, sublytic level of C5b-9) may also be involved in pro- as well as anti-inflammatory activities. Moreover, we discuss evidence suggesting that local C activation may contribute to tissue remodelling activities during repair in the CNS.