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Review
. 2015 Jan;35(1):71-83.
doi: 10.1007/s10571-014-0101-6. Epub 2014 Aug 23.

Microglial Aβ receptors in Alzheimer's disease

Yang Yu  1 , Richard D Ye
Affiliations
Review

Microglial Aβ receptors in Alzheimer's disease

Yang Yu et al. Cell Mol Neurobiol. 2015 Jan.

Abstract

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.

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Figures

Fig. 1
Fig. 1
The structures and functions of microglia Aβ receptors. SCARA has a collagen-like domain, which is essential for ligand binding. SCARB has two transmembrane domains. RAGE is a transmembrane receptor of the immunoglobulin super family. GPCRs are known as seven-transmembrane domain receptors. CD14 anchors to the membrane and acts as a co-receptor along with the TLR2 or TLR4 for interaction with Aβ. TLRs are single membrane spanning and these two TLRs are believed to function as dimers. 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 and FPR2 display both functions. Additionally, the exact roles of MARCO and SCARB-1 in microglia following Aβ binding need further investigation
See this image and copyright information in PMC

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