Microglial Aβ Receptors in Alzheimer’s Disease
Microglial Aβ Receptors in Alzheimer’s Disease
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DOI：
10.1007/s10571-014-0101-6
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发表时间：
2014-08
影响因子：
4
通讯作者：
Yang Yu;R. Ye
中科院分区：
文献类型：
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作者：
Yang Yu;R. Ye
淀粉样蛋白β (a β)通过其神经毒性和炎症作用在阿尔茨海默病（AD）的进展中起关键作用。一方面，Aβ与小胶质细胞结合并激活它们产生炎症介质。另一方面，Aβ通过受体介导的吞噬和降解被小胶质细胞清除。本文综述了结合Aβ并参与小胶质细胞活化和/或Aβ吞噬和清除的小胶质膜受体。这些受体可分为几类。清道夫受体（SRs）包括清道夫受体A-1 （SCARA-1）、MARCO、清道夫受体B-1 （SCARB-1）、CD36和晚期糖基化终产物受体（RAGE）。G蛋白偶联受体（gpcr）是甲酰基肽受体2 （FPR2）和趋化因子样受体1 （CMKLR1）。还有toll样受体（tlr），包括TLR2、TLR4和共受体CD14。功能上，SCARA-1和CMKLR1参与Aβ的摄取，RAGE负责小胶质细胞的激活和Aβ结合后促炎介质的产生。CD36、CD36/CD47/α6β1-intergrin、CD14/TLR2/TLR4和FPR2均具有上述两种功能。此外，MARCO和SCARB-1也表现出结合Aβ的能力，并可能参与AD的进展。在这里，我们重点关注这些受体在小胶质细胞中的表达和分布，以及它们在小胶质细胞与Aβ相互作用中的作用。最后，我们讨论了这些受体在AD中的潜在治疗价值。
Amyloid β (Aβ) plays a pivotal role in the progression of Alzheimer’s disease (AD) through its neurotoxic and inflammatory effects. On one hand, Aβ binds to microglia and activates them to produce inflammatory mediators. On the other hand, Aβ is cleared by microglia through receptor-mediated phagocytosis and degradation. This review focuses on microglial membrane receptors that bind Aβ and contribute to microglial activation and/or Aβ phagocytosis and clearance. These receptors can be categorized into several groups. The scavenger receptors (SRs) include scavenger receptor A-1 (SCARA-1), MARCO, scavenger receptor B-1 (SCARB-1), CD36 and the receptor for advanced glycation end product (RAGE). The G protein-coupled receptors (GPCRs) are formyl peptide receptor 2 (FPR2) and chemokine-like receptor 1 (CMKLR1). There are also toll-like receptors (TLRs) including TLR2, TLR4, and the co-receptor CD14. Functionally, SCARA-1 and CMKLR1 are involved in the uptake of Aβ, and RAGE is responsible for the activation of microglia and production of proinflammatory mediators following Aβ binding. CD36, CD36/CD47/α6β1-intergrin, CD14/TLR2/TLR4, and FPR2 display both functions. Additionally, MARCO and SCARB-1 also exhibit the ability to bind Aβ and may be involved in the progression of AD. Here, we focus on the expression and distribution of these receptors in microglia and their roles in microglia interaction with Aβ. Finally, we discuss the potential therapeutic value of these receptors in AD.