Fatoba Oluwaseun, Itokazu Takahide, Yamashita Toshihide
Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Japan.
WPI-Immunology Frontier Research Center, Osaka University, Suita, Japan.
FEBS J. 2022 Apr;289(8):2085-2109. doi: 10.1111/febs.15772. Epub 2021 Mar 1.
The complement system, an essential tightly regulated innate immune system, is a key regulator of normal central nervous system (CNS) development and function. However, aberrant complement component expression and activation in the brain may culminate into marked neuroinflammatory response, neurodegenerative processes and cognitive impairment. Over the years, complement-mediated neuroinflammatory responses and complement-driven neurodegeneration have been increasingly implicated in the pathogenesis of a wide spectrum of CNS disorders. This review describes how complement system contributes to normal brain development and function. We also discuss how pathologic insults such as misfolded proteins, lipid droplet/lipid droplet-associated protein or glycosaminoglycan accumulation could trigger complement-mediated neuroinflammatory responses and neurodegenerative process in neurodegenerative proteinopathies, age-related macular degeneration and neurodegenerative lysosomal storage disorders.
补体系统是一个必需的受到严格调控的固有免疫系统，是正常中枢神经系统（CNS）发育和功能的关键调节因子。然而，大脑中补体成分的异常表达和激活可能最终导致明显的神经炎症反应、神经退行性变过程和认知障碍。多年来，补体介导的神经炎症反应和补体驱动的神经退行性变越来越多地被认为与多种中枢神经系统疾病的发病机制有关。本综述描述了补体系统如何促进正常脑发育和功能。我们还讨论了诸如错误折叠蛋白、脂滴/脂滴相关蛋白或糖胺聚糖积累等病理损伤如何在神经退行性蛋白病、年龄相关性黄斑变性和神经退行性溶酶体贮积症中引发补体介导的神经炎症反应和神经退行性变过程。
