The complement cascade is a critical effector mechanism of the innate immune system that contributes to the rapid clearance of pathogens and dead or dying cells, as well as contributing to the extent and limit of the inflammatory immune response. In addition, some of the early components of this cascade have been clearly shown to play a beneficial role in synapse elimination during the development of the nervous system, although excessive complement-mediated synaptic pruning in the adult or injured brain may be detrimental in multiple neurogenerative disorders. While many of these later studies have been in mouse models, observations consistent with this notion have been reported in human postmortem examination of brain tissue. Increasing awareness of distinct roles of C1q, the initial recognition component of the classical complement pathway, that are independent of the rest of the complement cascade, as well as the relationship with other signaling pathways of inflammation (in the periphery as well as the central nervous system), highlights the need for a thorough understanding of these molecular entities and pathways to facilitate successful therapeutic design, including target identification, disease stage for treatment, and delivery in specific neurologic disorders. Here, we review the evidence for both beneficial and detrimental effects of complement components and activation products in multiple neurodegenerative disorders. Evidence for requisite co-factors for the diverse consequences are reviewed, as well as the recent studies that support the possibility of successful pharmacological approaches to suppress excessive and detrimental complement-mediated chronic inflammation, while preserving beneficial effects of complement components, to slow the progression of neurodegenerative disease.

中文翻译：

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补体系统在神经退行性疾病中的好、坏和机会

补体级联是先天免疫系统的关键效应机制，有助于快速清除病原体和死亡或垂死的细胞，并有助于炎症免疫反应的程度和限制。此外，该级联的一些早期成分已明确显示在神经系统发育过程中在突触消除中发挥有益作用，尽管在成人或受伤大脑中过度补体介导的突触修剪可能对多发性神经元发育有害。障碍。虽然这些后来的许多研究都是在小鼠模型中进行的，但在人类死后脑组织检查中已经报道了与这一观点一致的观察结果。提高对 C1q（经典补体途径的初始识别成分）不同作用的认识，独立于补体级联的其余部分，以及与炎症的其他信号通路（在外周和中枢神经系统）的关系，强调需要彻底了解这些分子实体和通路，以促进成功的治疗设计，包括目标识别、治疗的疾病阶段和特定神经系统疾病的递送。在这里，我们回顾了补体成分和激活产物在多种神经退行性疾病中的有益和有害影响的证据。审查了导致各种后果的必要辅助因素的证据，以及最近的研究，这些研究支持成功的药理学方法抑制过度和有害的补体介导的慢性炎症的可能性，