Wang Qiu-Lin, Fang Chang-Le, Huang Xue-Yan, Xue Lu-Lu
Department of Clinical Medicine Chongqing Medical University Chongqing China.
Department of Anesthesiology Southwest Medical University Luzhou Sichuan China.
Ibrain. 2022 Mar 3;8(1):3-14. doi: 10.1002/ibra.12026. eCollection 2022 Spring.
Alzheimer's disease (AD) is a degenerative brain disease with complex clinical manifestations and pathogeneses such as abnormal deposition of beta-amyloid protein and inflammation caused by the excessive activation of microglia. CXC motif chemokine receptor type 4 (CXCR4) is a type of G protein-coupled receptor that binds to CXC motif ligand 12 (CXCL12) to activate downstream signaling pathways, such as the Janus kinase/signal transducer and activator of transcription and the renin-angiotensin system (Ras)/RAF proto-oncogene serine (Raf)/mitogen-activated protein kinase/extracellular-regulated protein kinase; most of these signaling pathways are involved in inflammatory responses. CXCR4 is highly expressed in the microglia and astrocytes; this might be one of the important causes of inflammation caused by microglia and astrocytes. In this review, we summarize the mechanism and therapeutics of AD, the structures of CXCR4 and the CXCL12 ligand, and the mechanisms of CXCR4/CXCL12 that are involved in the occurrence and development of AD. The possible treatment of AD through microglia and astrocytes is also discussed, with the aim of providing a new method for the treatment of AD.
阿尔茨海默病(AD)是一种具有复杂临床表现和发病机制的退行性脑疾病,如β-淀粉样蛋白异常沉积以及小胶质细胞过度活化引发的炎症。CXC基序趋化因子受体4(CXCR4)是一种G蛋白偶联受体,它与CXC基序配体12(CXCL12)结合以激活下游信号通路,如Janus激酶/信号转导子和转录激活子以及肾素-血管紧张素系统(Ras)/RAF原癌基因丝氨酸(Raf)/丝裂原活化蛋白激酶/细胞外调节蛋白激酶;这些信号通路大多参与炎症反应。CXCR4在小胶质细胞和星形胶质细胞中高表达;这可能是小胶质细胞和星形胶质细胞引发炎症的重要原因之一。在本综述中,我们总结了AD的机制和治疗方法、CXCR4和CXCL12配体的结构,以及CXCR4/CXCL12参与AD发生发展的机制。还讨论了通过小胶质细胞和星形胶质细胞治疗AD的可能性,旨在为AD的治疗提供一种新方法。