Microglial scavenger receptors and their roles in the pathogenesis of Alzheimer's disease.
Microglial scavenger receptors and their roles in the pathogenesis of Alzheimer's disease.
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DOI：
10.1155/2012/489456
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发表时间：
2012
影响因子：
--
通讯作者：
El Khoury J
中科院分区：
文献类型：
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作者：
Wilkinson K;El Khoury J
随着人口老龄化，阿尔茨海默病（AD）的患病率正在增加。AD患者脑中淀粉样蛋白-β（Aβ）的沉积是该疾病的标志，并与小胶质细胞数量和激活状态增加相关。小胶质细胞与Aβ的相互作用似乎在AD发病机制中起着双重作用。一方面，小胶质细胞可以吞噬和清除Aβ，但小胶质细胞与Aβ的结合也会增加其产生炎性细胞因子、趋化因子和神经毒性活性氧自由基（ROS）的能力。清道夫受体（Scavenger receptor）是一组表达于小胶质细胞表面的进化上保守的蛋白质，作为Aβ的受体发挥作用。特别感兴趣的是SCARA-1（清道夫受体A-1）、CD 36和CD 34（晚期糖基化终产物受体）。SCARA-1似乎参与了Aβ的清除，而CD 36和CD 34参与了Aβ对小胶质细胞的激活。在这篇综述中，我们讨论了各种清道夫受体在小胶质细胞与Aβ相互作用中的作用，并提出这些受体在AD病理学的发展中发挥互补的非冗余功能。我们还讨论了这些受体在AD中的潜在治疗应用。
Alzheimer's disease (AD) is increasing in prevalence with the aging population. Deposition of amyloid-β (Aβ) in the brain of AD patients is a hallmark of the disease and is associated with increased microglial numbers and activation state. The interaction of microglia with Aβ appears to play a dichotomous role in AD pathogenesis. On one hand, microglia can phagocytose and clear Aβ, but binding of microglia to Aβ also increases their ability to produce inflammatory cytokines, chemokines, and neurotoxic reactive oxygen species (ROS). Scavenger receptors, a group of evolutionally conserved proteins expressed on the surface of microglia act as receptors for Aβ. Of particular interest are SCARA-1 (scavenger receptor A-1), CD36, and RAGE (receptor for advanced glycation end products). SCARA-1 appears to be involved in the clearance of Aβ, while CD36 and RAGE are involved in activation of microglia by Aβ. In this review, we discuss the roles of various scavenger receptors in the interaction of microglia with Aβ and propose that these receptors play complementary, nonredundant functions in the development of AD pathology. We also discuss potential therapeutic applications for these receptors in AD.