Innate immunity in Alzheimer's disease: a complex affair.
Innate immunity in Alzheimer's disease: a complex affair.
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DOI：
10.2174/1871527311312050008
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发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
Town T
中科院分区：
文献类型：
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作者：
Guillot-Sestier MV;Town T
阿尔茨海默病(AD)具有三个主要的组织病理学特征：β-淀粉样斑块、神经原纤维缠结和胶质增生。虽然几十年来一直被忽视，但由小胶质细胞协调的神经炎症过程现在被认为是AD演变中的病因事件。小胶质细胞位于淀粉样斑块附近，表现出由多种细胞因子、趋化因子和天然免疫细胞表面受体的表达决定的各种激活表型。在AD的病理发展过程中，小胶质细胞不能限制淀粉样斑块的形成，可能导致神经毒性和认知功能障碍。然而，在特定条件下，小胶质细胞可以参与大脑淀粉样蛋白的清除。这篇综述着重于小胶质细胞与Aβ病理之间的复杂关系，并强调了小胶质细胞激活在AD背景下的有害和有益作用。对小胶质细胞生物学的深入了解将有望为下一代AD治疗方法铺平道路，旨在利用这些神秘的中枢神经系统天然免疫细胞。
Alzheimer’s disease (AD) is characterized by three major histopathological hallmarks: β-amyloid plaques, neurofibrillary tangles and gliosis. While neglected for decades, neuroinflammatory processes coordinated by microglia are now accepted as etiologic events in AD evolution. Microglial cells are found in close vicinity to amyloid plaques and display various activation phenotypes determined by expression of a wide range of cytokines, chemokines, and innate immune cell surface receptors. During the development of AD pathology, microglia fail to restrict amyloid plaques and may contribute to neurotoxicity and cognitive deficit. Nevertheless, under specific conditions, microglia can participate in cerebral amyloid clearance. This review focuses on the complex relationship between microglia and Aβ pathology, and highlights both deleterious and beneficial roles of microglial activation in the context of AD. A deeper understanding of microglial biology will hopefully pave the way for next-generation AD therapeutic approaches aimed at harnessing these enigmatic innate immune cells of the central nervous system.