Druart Mélanie, Le Magueresse Corentin
INSERM UMR-S 1270, Paris, France.
Science and Engineering Faculty, Sorbonne Université, Paris, France.
Front Psychiatry. 2019 Aug 21;10:573. doi: 10.3389/fpsyt.2019.00573. eCollection 2019.
The complement system consists of more than 30 proteins that have long been known to participate to the immune defence against pathogens and to the removal of damaged cells. Their role, however, extends beyond immunity and clearance of altered "self" components in the periphery. In particular, complement proteins can be induced by all cell types in the brain. Recent discoveries highlight the role of complement in normal and pathological brain development. Specifically, the complement system mediates synaptic pruning, a developmental process whereby supernumerary synapses are eliminated in the immature brain. The complement system has been implicated in pathological synapse elimination in schizophrenia, West Nile virus infection, and lupus, all of which are associated with psychiatric manifestations. Complement also contributes to synapse loss in neurodegenerative conditions. This review provides a brief overview of the well-studied role of complement molecules in immunity. The contribution of complement to embryonic and adult neurogenesis, neuronal migration, and developmental synaptic elimination in the normal brain is reviewed. We discuss the role of complement in synapse loss in psychiatric and neurological diseases and evaluate the therapeutic potential of complement-targeting drugs for brain disorders.
补体系统由30多种蛋白质组成，长期以来人们一直认为这些蛋白质参与针对病原体的免疫防御以及清除受损细胞。然而，它们的作用不仅限于外周免疫和清除改变的“自身”成分。特别是，大脑中的所有细胞类型都可以诱导补体蛋白。最近的发现突出了补体在正常和病理性脑发育中的作用。具体而言，补体系统介导突触修剪，这是一个发育过程，通过该过程未成熟大脑中多余的突触被消除。补体系统与精神分裂症、西尼罗河病毒感染和狼疮中的病理性突触消除有关，所有这些都与精神症状有关。补体也导致神经退行性疾病中的突触丧失。本综述简要概述了补体分子在免疫中已得到充分研究的作用。综述了补体对胚胎和成人神经发生、神经元迁移以及正常大脑中发育性突触消除的贡献。我们讨论了补体在精神和神经疾病中突触丧失中的作用，并评估了靶向补体的药物对脑部疾病的治疗潜力。
