小胶质细胞在肌萎缩侧索硬化症发病中的作用机制及其治疗策略
The Mechanism of Microglia in the Pathogenesis of Amyotrophic Lateral Sclerosis and Its Therapeutic Strategies
陈佑甲 1孔垂禧 1蔡招聘 2沈承勇 3金志刚1
作者信息
- 1. 浙江师范大学生命科学学院,金华 321004
- 2. 浙江师范大学生命科学学院,金华 321004;浙江大学转化医学研究院,杭州 310020
- 3. 浙江大学转化医学研究院,杭州 310020
- 折叠
摘要
肌萎缩侧索硬化症(amyotrophic lateral sclerosis,ALS)是一种多因素造成的神经退行性疾病,其特征是上下运动神经元变性导致肌无力、进行性麻痹和严重的功能障碍.ALS运动神经元损伤可由错误折叠蛋白聚集、神经炎症、谷氨酸兴奋毒性、铁过载和脱髓鞘等多种因素引起.近几年研究发现,小胶质细胞的活化是ALS神经病理学的重要标志之一,但其在ALS发病过程中的确切作用仍不清楚.小胶质细胞与运动神经元之间的平衡状态在运动神经元损伤中起到了保护作用,并促进了神经再生.然而,随着遗传和环境等因素的共同作用,运动神经元应激损伤可能加剧,并伴随小胶质细胞异常增殖和活化,不仅导致小胶质细胞介导的运动神经元保护和损伤修复功能的丧失,还促使小胶质细胞自身表型由抗炎和神经保护转变为促炎和神经毒性.此外,来自运动神经元的神经毒性信号诱导小胶质细胞产生炎症因子,进一步加剧运动神经元损伤,并促进运动神经元丢失和细胞死亡的恶性循环,从而加剧ALS疾病进展.该文将简要概述和讨论小胶质细胞在ALS中的病理作用及其潜在靶向治疗策略.
Abstract
ALS(amyotrophic lateral sclerosis)is a multifactorial neurodegenerative disease character-ized by the degeneration of upper and lower motor neurons leading to muscle weakness,progressive paralysis and severe functional impairment.ALS motor neuron damage is caused by a variety of factors including misfolded protein aggregation,neuroinflammation,glutamate excitotoxicity,iron overload,and demyelination.Recent studies have found that the activation of microglia is one of the important hallmarks of ALS neuropathology,but its pre-cise role in the pathogenesis of ALS remains unclear.The balance between microglia and motor neurons executes a protective effect in motor neuron damage and promotes neurogenesis.However,along the combination of genetic,environmental and other factors,stress-induced motor neuron damage is further exacerbated,concomitant with abnormal proliferation and activation of microglia.Thus,microglia not only lose their ability in motor neuron pro-tection and injury repair,but also is switched from anti-inflammation and neuroprotection to pro-inflammation and neurotoxicity in phenotype.Besides,neurotoxic signaling from motor neurons induces microglia to produce inflam-matory factors,further increases motor neuron damage,and promotes the motor neuron loss and vicious circle of cell death,thereby exacerbating the ALS progression.This review will briefly summarize and discuss the pathologi-cal role of microglia in ALS and its potential targeted therapy strategies.
关键词
小胶质细胞/肌萎缩侧索硬化症/神经退行性疾病Key words
microglia/amyotrophic lateral sclerosis/neurodegenerative diseases引用本文复制引用
出版年
2024
NETL
NSTL
万方数据