轻度认知障碍神经炎症机制的作用靶点

Mechanisms of neuroinflammation in mild cognitive impairment

背景:临床上,轻度认知障碍是正常衰老认知下降与阿尔茨海默症早期之间的过渡状态,被认为是预防或改变阿尔茨海默症退行性变的最佳阶段。近年来,越来越多的研究表明,神经炎症是轻度认知障碍的核心发病机制和主要早期病理特征之一。目的:综述国内外神经炎症导致轻度认知障碍的机制研究进展。方法:英文检索词为“neuroinflammation,mild cognitive impairment,proinflammatory cytokines,microglia,astroglia,NLRP3,NF-κB,TNF-α,CD40”,中文检索词为“神经炎症,轻度认知障碍,促炎细胞因子,小胶质细胞,星形胶质细胞,NLRP3炎症小体,核因子κB,肿瘤坏死因子α,白细胞分化抗原40”,检索2000至2020年PubMed、CNKI、万方数据库中收录的轻度认知障碍神经炎症机制研究的相关文献,进行总结分析。结果与结论:①由一系列复杂的因素,例如糖尿病、肥胖症和脑创伤等引起的慢性系统性炎症,以及脑内β-淀粉样蛋白沉积、能量代谢障碍和衰老引起的神经元、脑内细胞死亡等,共同导致脑内神经炎症的产生并且激活胶质细胞,被激活的胶质细胞持续释放肿瘤坏死因子α、NLRP3、核因子κB、CD40等炎症因子,造成脑内神经元、突触等受到损伤,最终导致认知功能受损;②因此调节神经炎症有望成为轻度认知障碍有效的治疗策略。

BACKGROUND:Clinically,mild cognitive impairment is a transitional state between the normal aging and Alzheimer’s disease,which is considered to be an appropriate stage to prevent or change the progressive degeneration of Alzheimer’s disease.In recent years,increasing studies have shown that neuroinflammation is the core pathogenesis and one of the main early pathological features of mild cognitive impairment.OBJECTIVE:To review the global research progress in the mechanisms of neuroinflammation leading to mild cognitive impairment.METHODS:Using“neuroinflammation,mild cognitive impairment,proinflammatory cytokines,microglia,astroglia,NLRP3,NF-κB,TNF-α,CD40”as the key words in English and Chinese,respectively,we retrieved the related literatures on the neuroinflammation mechanism of mild cognitive impairment from 2000 to 2020 in PubMed,CNKI,and WanFang databases.RESULTS AND CONCLUSION:A series of complex factors will cause neuroinflammation,such as chronic systemic inflammation caused by brain trauma,diabetes and obesity,energy metabolism disorders in the brain,β-amyloid protein deposition and aging.Neuroinflammation will activate glial cells in the central nervous system.Activated glial cells will continuously release inflammatory factors,such as tumor necrosis factor-α,NLRP3,nuclear factor-κB,and CD40 to damage neurons and synapses,which damage neurons and axons in the brain,and eventually lead to cognitive dysfunction.Therefore,regulating neuroinflammation is expected to become an effective treatment strategy for mild cognitive impairment.