The receptor for advanced glycation endproducts (RAGE) is an ubiquitous, transmembrane, immunoglobulin-like receptor that exists in multiple isoforms and binds to a diverse range of endogenous extracellular ligands and intracellular effectors. Ligand binding at the extracellular domain of RAGE initiates a complex intracellular signaling cascade, resulting in the production of reactive oxygen species (ROS), immunoinflammatory effects, cellular proliferation, or apoptosis with concomitant upregulation of RAGE itself. To date, research has mainly focused on the correlation between RAGE activity and pathological conditions, such as cancer, diabetes, cardiovascular diseases, and neurodegeneration. Because RAGE plays a role in many pathological disorders, it has become an attractive target for the development of inhibitors at the extracellular and intracellular domains. This review describes the role of endogenous RAGE ligands/effectors in normo- and pathophysiological processes, summarizes the current status of exogenous small-molecule inhibitors of RAGE and concludes by identifying key strategies for future therapeutic intervention.

中文翻译：

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针对受体的高级糖基化终产物（RAGE）：药物化学的观点

晚期糖基化终产物（RAGE）的受体是一种普遍存在的跨膜，免疫球蛋白样受体，存在多种同种型，并与多种内源性细胞外配体和细胞内效应子结合。RAGE胞外域上的配体结合会启动复杂的细胞内信号传导级联反应，从而导致活性氧（ROS）的产生，免疫炎症作用，细胞增殖或细胞凋亡，并伴有RAGE本身的上调。迄今为止，研究主要集中在RAGE活动与病理状况之间的相关性，例如癌症，糖尿病，心血管疾病和神经变性。由于RAGE在许多病理性疾病中都起着作用，它已成为开发细胞外和细胞内域抑制剂的有吸引力的靶标。这篇综述描述了内源性RAGE配体/效应物在正常和病理生理过程中的作用，总结了外源性RAGE小分子抑制剂的现状，并通过确定未来治疗干预的关键策略得出了结论。