C1q, the initiator of the classical pathway of the complement system, is activated during Alzheimer’s disease (AD) development and progression and is especially associated with the production and deposition of β-amyloid protein (Aβ) and phosphorylated tau in β-amyloid plaques (APs) and neurofibrillary tangles (NFTs). Activation of C1q is responsible for induction of synapse loss, leading to neurodegeneration in AD. Mechanistically, C1q could activate glial cells, which results in the loss of synapses via regulation of synapse pruning and phagocytosis in AD. In addition, C1q induces neuroinflammation by inducing proinflammatory cytokine secretion, which is partially mediated by inflammasome activation. Activation of inflammasomes might mediate the effects of C1q on induction of synapse apoptosis. On the other hand, activation of C1q impairs mitochondria, which hinders the renovation and regeneration of synapses. All these actions of C1q contribute to the loss of synapses during neurodegeneration in AD. Therefore, pharmacological, or genetic interventions targeting C1q may provide potential therapeutic strategies for combating AD.

Graphical Abstract

中文翻译：

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作为潜在的治疗靶点，C1q 通过炎症小体激活细胞凋亡和线粒体损伤机制诱导突触丢失，从而治疗阿尔茨海默病

C1q 是补体系统经典途径的启动子，在阿尔茨海默病 (AD) 的发生和进展过程中被激活，尤其与 β-淀粉样蛋白 (Aβ) 和 β-淀粉样斑块中磷酸化 tau 的产生和沉积相关。 AP）和神经原纤维缠结（NFT）。C1q 的激活会导致突触丢失，从而导致 AD 中的神经变性。从机制上讲，C1q 可以激活神经胶质细胞，从而通过调节 AD 中的突触修剪和吞噬作用导致突触丢失。此外，C1q 通过诱导促炎细胞因子分泌来诱导神经炎症，这部分是由炎症小体激活介导的。炎症小体的激活可能介导 C1q 对突触凋亡诱导的影响。另一方面，C1q 的激活会损害线粒体，从而阻碍突触的更新和再生。C1q 的所有这些作用都会导致 AD 神经变性过程中突触的丧失。因此，针对 C1q 的药理学或遗传干预可能为对抗 AD 提供潜在的治疗策略。

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