Department of Biotechnology, PSG College of Technology, Coimbatore, Tamil Nadu, India.
Curr Alzheimer Res. 2020;17(14):1262-1279. doi: 10.2174/1567205018666210218164246.
Receptor for Advanced Glycation End product (RAGE) plays a crucial role in a variety of physiological and pathological processes due to its ability to bind a broad repertory of ligands. There are also multiple forms of RAGE that exist; some work on promoting feed-forward pathways while others perform inhibitory actions. This review focuses on the RAGE isoforms expression, its intracellular pathways activation via RAGE- ligand interaction, and its importance in the physiological and pathological process of the brain. Many studies have suggested that RAGE induces the pathophysiological changes in Alzheimer's disease (AD) by being an intermediator of inflammation and inducer of oxidative stress. The critical roles played by RAGE in AD include its involvement in amyloid-beta (Aβ) production, clearance, synaptic impairment, and neuronal circuit dysfunction. RAGE-Aβ interaction also mediates the bi-directional crosstalk between peripheral and central systems. This interaction underlies a potential molecular pathway that disrupts the material structure and physiology of the brain. This review highlights the structure-function relation for RAGEAβ interaction and the role of RAGE as a potential target in the development of treatments for AD.
晚期糖基化终产物受体（RAGE）因其能够结合广泛的配体而在多种生理和病理过程中发挥关键作用。RAGE 也存在多种形式，有些促进正反馈途径，而另一些则起抑制作用。本综述重点介绍了 RAGE 异构体的表达、通过 RAGE-配体相互作用激活其细胞内途径，以及其在大脑生理和病理过程中的重要性。许多研究表明，RAGE 通过作为炎症的中介和氧化应激的诱导物，在阿尔茨海默病（AD）中引起病理生理变化。RAGE 在 AD 中的关键作用包括参与淀粉样蛋白-β（Aβ）的产生、清除、突触损伤和神经元回路功能障碍。RAGE-Aβ 相互作用还介导了外周和中枢系统之间的双向串扰。这种相互作用为破坏大脑物质结构和生理学的潜在分子途径提供了基础。本综述强调了 RAGE-Aβ 相互作用的结构-功能关系以及 RAGE 作为 AD 治疗开发的潜在靶点的作用。
