The functions of the complement system to both innate and adaptive immunity through opsonization, cell lysis, and inflammatory activities are well known. In contrast, the role of complement in the central nervous system (CNS) which extends beyond immunity, is only beginning to be recognized as important to neurodevelopment and neurodegeneration. In addition to protecting the brain against invasive pathogens, appropriate activation of the complement system is pivotal to the maintenance of normal brain function.
1. Introduction
The complement system is foundational to the innate immune response in defending the body against invading pathogens by phagocytosis or by the activation of the adaptive immune system. In the CNS, however, the complement system protects the brain from not only pathogens but other potentially harmful stimuli such as aberrant proteins and cellular debris
[1]. Findings from studies presented will show that complement components are produced by both neurons and glial cells. This local production of complement factors may be a developmental advantage as it enables a more rapid response than reliance on peripheral production and diffusion through the blood–brain barrier (BBB). Under normal circumstances, the activation of the complement system in the CNS consists of over 30 complement factors under tight regulation
[2]. However, when this well-tuned regulatory machinery malfunctions, aberrant complement factors can exacerbate neurological symptoms of brain conditions and accelerate the development of aging-related or neurodegenerative diseases
[3][4][5]. Emerging evidence suggests that higher levels of complement factors are present in developing and degenerating brains and perform novel functions in neurodevelopment and contribute to the pathophysiology of neurodegenerative diseases
[3][6][7][8]. Therefore, an understanding of endogenous complement production and regulation in the brain can provide insights into aberrant neurodevelopment and the genesis of neurodegeneration (
Table 1).
Table 1. Complement expression in the CNS and their role in neurodevelopment and neurodegeneration.