The role of microglia in amyloid clearance from the AD brain.
The role of microglia in amyloid clearance from the AD brain.
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DOI：
10.1007/s00702-010-0433-4
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发表时间：
2010-08
影响因子：
3.3
通讯作者：
Landreth, Gary E.
中科院分区：
文献类型：
--
作者：
Lee, C. Y. Daniel;Landreth, Gary E.
阿尔茨海默病（Alzheimer's disease，AD）是老年性痴呆的主要病因，其临床特征是细胞外β-淀粉样蛋白（β-amyloid，Aβ）沉积和细胞内神经元缠结。AD的发病机制是由脑内Aβ稳态的紊乱引起的，这一点已被广泛接受。Aβ通常在大脑中以高水平产生，并以相等的速率清除。因此，即使清除率中度降低也会导致Aβ蓄积和随后的淀粉样蛋白沉积。小胶质细胞是中枢神经系统（CNS）的组织巨噬细胞，在Aβ的内化和降解中发挥重要作用。Aβ以可溶性和纤维状形式存在于脑中。小胶质细胞以不同的方式与这两种形式的Aβ相互作用。通过巨胞饮作用和LDL受体相关蛋白（LRP）介导的途径摄取可溶性Aβ。Aβ的纤维形式与细胞表面先天免疫受体复合物相互作用，启动刺激吞噬作用的细胞内信号级联。炎症反应影响小胶质细胞的活化状态，并随后调节其摄取和降解Aβ的能力。ApoE及其受体已被证明在这些过程中发挥关键作用。本文就小胶质细胞清除Aβ的机制及其调控因子作一综述。
Alzheimer’s disease (AD), the most prominent cause of senile dementia, is clinically characterized by the extracellular deposition of β-amyloid (Aβ) and the intra-cellular neurofibrillary tangles. It has been well accepted that AD pathogenesis arises from perturbation in the homeostasis of Aβ in the brain. Aβ is normally produced at high levels in the brain and cleared in an equivalent rate. Thus, even a moderate decrease in the clearance leads to the accumulation of Aβ and subsequent amyloid deposition. Microglia are the tissue macrophages in the central nervous system (CNS) and have been shown to play major roles in internalization and degradation of Aβ. Aβ exists in the brain both in soluble and in fibrillar forms. Microglia interact with these two forms of Aβ in different ways. They take up soluble forms of Aβ through macropinocytosis and LDL receptor-related proteins (LRPs) mediated pathway. Fibrillar forms of Aβ interact with the cell surface innate immune receptor complex, initiating intracellular signaling cascades that stimulate phagocytosis. Inflammatory responses influence the activation status of microglia and subsequently regulate their ability to take up and degrade Aβ. ApoE and its receptors have been shown to play critical roles in these processes. In this review, we will explore the mechanisms that microglia utilize to clear Aβ and the effectors that modulate the processes.
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DOI：
10.1016/s1388-1981(99)00196-1
发表时间：
2000-02-24
影响因子：
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作者：
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