Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
WIREs Mech Dis. 2022 May;14(3):e1545. doi: 10.1002/wsbm.1545. Epub 2021 Nov 4.
Synapse elimination, also known as synaptic pruning, is a critical step in the maturation of neural circuits during brain development. Mounting evidence indicates that the complement cascade of the innate immune system plays an important role in synapse elimination. Studies indicate that excess synapses during development are opsonized by complement proteins and subsequently phagocytosed by microglia which expresses complement receptors. The process is regulated by diverse molecular signals, including complement inhibitors that affect the activation of complement, as well as signals that affect microglial recruitment and activation. These signals may promote or inhibit the removal of specific sets of synapses during development. The complement-microglia system has also been implicated in the pathogenesis of several developmental brain disorders, suggesting that the dysregulation of mechanisms of synapse pruning may underlie the specific circuitry defects in these diseases. Here, we review the latest evidence on the molecular and cellular mechanisms of complement-dependent and microglia-dependent synapse elimination during brain development, and highlight the potential of this system as a therapeutic target for developmental brain disorders. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology Neurological Diseases > Stem Cells and Development Immune System Diseases > Molecular and Cellular Physiology.
突触消除，也称为突触修剪，是大脑发育过程中神经回路成熟的关键步骤。越来越多的证据表明，先天免疫系统的补体级联反应在突触消除中发挥重要作用。研究表明，发育过程中多余的突触被补体蛋白调理，随后被表达补体受体的小胶质细胞吞噬。这个过程受到多种分子信号的调节，包括影响补体激活的补体抑制剂，以及影响小胶质细胞募集和激活的信号。这些信号可能促进或抑制发育过程中特定突触集合的去除。补体-小胶质细胞系统也与几种发育性脑疾病的发病机制有关，这表明突触修剪机制的失调可能是这些疾病特定电路缺陷的基础。在这里，我们综述了补体依赖性和小胶质细胞依赖性突触消除在大脑发育过程中的分子和细胞机制的最新证据，并强调了该系统作为发育性脑疾病治疗靶点的潜力。本文属于以下分类：神经疾病 > 分子和细胞生理学神经疾病 > 干细胞与发育免疫系统疾病 > 分子和细胞生理学。
