Cai Zhiyou, Hussain M Delwar, Yan Liang-Jun
1Department of Neurology, The Lu'an Affiliated Hospital of Anhui Medical University , Lu'an People's Hospital, Lu'an, Anhui Province , China.
Int J Neurosci. 2014 May;124(5):307-21. doi: 10.3109/00207454.2013.833510. Epub 2013 Sep 12.
Compelling evidence from basic molecular biology has demonstrated the dual roles of microglia in the pathogenesis of Alzheimer's disease (AD). On one hand, microglia are involved in AD pathogenesis by releasing inflammatory mediators such as inflammatory cytokines, complement components, chemokines, and free radicals that are all known to contribute to beta-amyloid (Aβ) production and accumulation. On the other hand, microglia are also known to play a beneficial role in generating anti-Aβ antibodies and stimulating clearance of amyloid plaques. Aβ itself, an inducer of microglia activation and neuroinflammation, has been considered as an underlying and unifying factor in the development of AD. A vicious cycle of inflammation has been formed between Aβ accumulation, activated microglia, and microglial inflammatory mediators, which enhance Aβ deposition and neuroinflammation. Thus, inhibiting the vicious cycle seems to be a promising treatment to restrain further development of AD. With increasing research efforts on microglia in AD, intervention of microglia activation and neuroinflammation in AD may provide a potential target for AD therapy in spite of the provisional failure of nonsteroidal antiinflammatory drugs in clinical trials.
基础分子生物学的有力证据表明，小胶质细胞在阿尔茨海默病（AD）发病机制中具有双重作用。一方面，小胶质细胞通过释放炎症介质（如炎症细胞因子、补体成分、趋化因子和自由基）参与AD发病机制，这些炎症介质均已知会促进β-淀粉样蛋白（Aβ）的产生和积累。另一方面，小胶质细胞在产生抗Aβ抗体和刺激淀粉样斑块清除方面也发挥有益作用。Aβ本身是小胶质细胞激活和神经炎症的诱导剂，被认为是AD发展的一个潜在统一因素。在Aβ积累、活化的小胶质细胞和小胶质细胞炎症介质之间形成了炎症恶性循环，这会增强Aβ沉积和神经炎症。因此，抑制这种恶性循环似乎是抑制AD进一步发展的一种有前景的治疗方法。随着对AD中小胶质细胞研究的不断深入，尽管非甾体抗炎药在临床试验中暂时失败，但干预AD中小胶质细胞的激活和神经炎症可能为AD治疗提供一个潜在靶点。
