β-amyloid, microglia, and the inflammasome in Alzheimer's disease.
β-amyloid, microglia, and the inflammasome in Alzheimer's disease.
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DOI：
10.1007/s00281-015-0518-0
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发表时间：
2015-11
影响因子：
9
通讯作者：
El Khoury J
中科院分区：
文献类型：
--
作者：
Gold M;El Khoury J
大量证据表明，单核巨噬细胞包括小胶质细胞、单核细胞和巨噬细胞在脑内淀粉样蛋白(β-β，Aβ)沉积部位聚集是阿尔茨海默病(AD)及相关动物模型的重要病理特征，聚集在A淀粉样沉积周围的单核巨噬细胞的浓度是大脑邻近区域的数倍。小胶质细胞吞噬和清除碎片、病原体和毒素，但它们也可以被激活以产生炎性细胞因子、趋化因子和神经毒素。在过去的十年中，小胶质细胞在AD中的作用已经开始被阐明，我们提出这些细胞在AD的发病机制中起着二分性的作用。小胶质细胞能够清除可溶性和纤维状的Aβ，但这些细胞与Aβ的持续相互作用可导致炎症反应，从而导致神经毒性。炎性小体是一种可诱导的高分子量蛋白质复合体，参与多种炎症病理过程。最近，β被发现在体外和体内激活小胶质细胞中的NLRP3炎症体，从而定义了一条导致AD进展的新途径。在这篇手稿中，我们回顾了导致Aβ诱导的炎症体激活的可能步骤，并讨论了这如何有助于AD的发病机制。
There is extensive evidence that accumulation of mononuclear phagocytes including microglial cells, monocytes and macrophages at sites of β-amyloid (Aβ) deposition in the brain is an important pathological feature of Alzheimer’s disease (AD) and related animal models, and the concentration of these cells clustered around Aβ deposits is several folds higher than in neighboring areas of the brain. Microglial cells phagocytose and clear debris, pathogens and toxins, but they can also be activated to produce inflammatory cytokines, chemokines and neurotoxins. Over the past decade, the roles of microglial cells in AD have begun to be clarified and we proposed that these cells play a dichotomous role in the pathogenesis of AD. Microglial cells are able to clear soluble and fibrillar Aβ, but continued interactions of these cells with Aβ can lead to an inflammatory response resulting in neurotoxicity. Inflammasomes are inducible high molecular weight protein complexes that are involved in many inflammatory pathological processes. Recently, Aβ was found to activate the NLRP3 inflammasome in microglial cells in vitro and in vivo thereby defining a novel pathway that could lead to progression of AD. In this manuscript we review possible steps leading to Aβ-induced inflammasome activation and discuss how this could contribute to the pathogenesis of AD.