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过程工程学报 ›› 2018, Vol. 18 ›› Issue (5): 900-907.DOI: 10.12034/j.issn.1009-606X.218206

• 中科院过程工程所60周年特邀 • 上一篇    下一篇

小胶质细胞对阿尔兹海默病发生发展的影响作用

刘小歌1,2, 张 伦1,2, 于晓琳1*   

  1. 1. 中国科学院过程工程研究所生化工程国家重点实验室,北京 100190 
    2. 中国科学院大学化学与化工学院,北京 100049
  • 收稿日期:2018-05-17 修回日期:2018-06-22 出版日期:2018-10-22 发布日期:2018-10-12
  • 通讯作者: 于晓琳 yuxiaolin@ipe.ac.cn
  • 基金资助:
    国家重大新药创制专项;国家重大新药创制专项;战略性先导科技专项

The role of microglia in Alzheimer's disease

Xiaoge LIU1,2,  Lun ZHANG1,2,  Xiaolin YU1*   

  1. 1. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190,China 
    2. School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
  • Received:2018-05-17 Revised:2018-06-22 Online:2018-10-22 Published:2018-10-12

摘要: 阿尔兹海默病(老年性痴呆,AD)是由β淀粉样蛋白(Aβ)和微管相关蛋白(Tau)聚集形成的具有毒性作用的寡聚物而引起的老年人主要以记忆力下降和脑部形成老年斑、神经纤维缠绕为特征的神经退行性疾病. 小胶质细胞作为中枢神经系统中的固有免疫细胞,是脑内免疫监视的关键成分,发挥内源性免疫防御作用. 正常生理状态的小胶质细胞能有效吞噬和清除毒性Aβ寡聚体,阻止AD发生. 在AD病理过程中,过度激活的小胶质细胞通过补体依赖途径过度吞噬突触,导致突触丧失,同时大量释放炎症因子,促进Tau相关病理变化,对神经元造成直接损伤,导致认知功能下降. 由此可见,小胶质细胞在AD发生发展过程中起着双刃剑的作用,探明小胶质细胞的极化状态及其在AD疾病机理中的作用将为攻克AD的药物研发提供突破性思路.

关键词: 小胶质细胞, 阿尔兹海默病, β淀粉样蛋白, 突触, 神经炎症

Abstract: Microglia, the innate immune cells of the central nervous system (CNS), serve as resident phagocytes that dynamically survey the environment and play crucial roles in CNS health and disease. Various roles are emerging for microglia in the healthy brain, from sculpting developing neuronal circuits to guiding neural plasticity. Understanding the physiological functions of microglia is important to evaluate their roles in disease. At pathological state, conditions associated with loss of cerebral homeostasis induce several dynamic microglial processes, including changes of cellular morphology, surface phenotype, secretory inflammatory mediators and proliferative responses, termed as an “activated state”. Activation and proliferation of microglia in the brain represents a prominent feature of several neurodegenerative diseases including Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder that is the most common cause of dementia, which is defined as a significant, persistent, and progressive memory loss combined with cognitive impairment and personality change. The key features of AD pathology are amyloid plaques by extracellular accumulation of amyloid-β (Aβ) and intracellular neurofibrillary tangles composed of tau proteins. There is mounting evidence that microglia protect against the incidence of AD, as impaired microglial activities and altered microglial responses to Aβ are associated with increased AD risk. In CNS, microglia have protective functions by phagocytosis and clearance of toxic Aβ oligomers, which prevent the development of AD. Once activated, microglia can mediate synapse loss by engulfment of synapses via a complement-dependent mechanism, secrete inflammatory factors and exacerbate tau pathology, resulting in the neuron injury and cognitive deficits. Therefore, microglia show the double-edged sword function in AD pathogenesis. Understanding the multiple states of microglial activation and their roles in AD pathology will provide breakthrough ideas for developing AD therapeutic strategies. In this review, the role of microglia in the pathogenesis of AD and the modulation of microglia activity as a therapeutic potential will be discussed.

Key words: Microglia, Alzheimer's disease, amyloid-β, synapse, Neuroinflammation