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小胶质细胞和单核细胞趋化因子及其受体在调节阿尔茨海默病相关淀粉样β蛋白和tau蛋白病变中的作用

Roles of Microglial and Monocyte Chemokines and Their Receptors in Regulating Alzheimer's Disease-Associated Amyloid-β and Tau Pathologies.

作者信息

Guedes Joana R, Lao Taotao, Cardoso Ana L, El Khoury Joseph

机构信息

Doctoral Programme in Experimental Biology and Biomedicine, CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.

Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.

出版信息

Front Neurol. 2018 Aug 14;9:549. doi: 10.3389/fneur.2018.00549. eCollection 2018.

Abstract

Chemokines and their receptors have been shown to affect amyloid-β (Aβ) and tau pathologies in mouse models of Alzheimer's disease (AD) by regulating microglia and monocyte-associated neuroinflammation, microglial movement and monocyte recruitment into the brain. These cells in turn can promote and mediate Aβ phagocytosis and degradation and tau phosphorylation. In this review we discuss published work in this field in mouse models of AD and review what is known about the contributions of microglial and monocyte chemokines and their receptors to amyloid and tau pathologies. We focus on the roles of the chemokine/chemokine receptor pairs CCL2/CCR2, CX3CL1/CX3CR1, CCL5/CCR5, CXCL10/CXCR3 and CXCL1/CXCR2, highlighting important knowledge gaps in this field. A full understanding of the functions of chemokines and their receptors in AD may guide the development of novel immunotherapies for this devastating disease.

摘要

趋化因子及其受体已被证明,在阿尔茨海默病(AD)小鼠模型中,通过调节小胶质细胞和单核细胞相关的神经炎症、小胶质细胞运动以及单核细胞向脑内募集,影响淀粉样β蛋白(Aβ)和tau蛋白病变。反过来,这些细胞可促进和介导Aβ的吞噬与降解以及tau蛋白磷酸化。在本综述中,我们讨论了该领域在AD小鼠模型中的已发表研究,并回顾了关于小胶质细胞和单核细胞趋化因子及其受体对淀粉样蛋白和tau蛋白病变作用的已知情况。我们重点关注趋化因子/趋化因子受体对CCL2/CCR2、CX3CL1/CX3CR1、CCL5/CCR5、CXCL10/CXCR3和CXCL1/CXCR2的作用,突出该领域重要的知识空白。全面了解趋化因子及其受体在AD中的功能,可能会为这种毁灭性疾病的新型免疫疗法开发提供指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6c0/6104478/8dc689eb696f/fneur-09-00549-g0001.jpg

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