Receptor for Advanced Glycation End Products as a Mediator of Inflammation and Oxidative Stress

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The receptor for advanced glycation end products (RAGEs) is a cell surface immunoglobulin class of molecules. RAGE prevails as a multiligand receptor capable of interacting with various ligands, the prominent amongst which is "advanced glycation end products (AGE)". The ligand-RAGE axis leads to an aggravated extent of inflammation and oxidative stress, activating various pro-inflammatory and prooxidative transcription factors such as nuclear factor kappa B (NF-κB). The binding of NF-κB to the promoter region of the RAGE gene activates its transcription. Once expressed, RAGE interacts further with its multiple ligands including AGE, HMGB1, S100, etc., culminating in aggravated inflammatory and oxidative stress. Thus, RAGE which is a product of an increased level of inflammation and oxidative stress, once produced perpetuates a brutal cycle of self-propagation through sustained interaction with various ligands and subsequent inflammation and oxidation stress. Several levels of crosstalk possibilities prevail between pro-inflammatory and prooxidative reactive molecules. Sustaining a high level of pro-inflammatory and prooxidative reactions is the basic requirement to complicate various non-communicable disease conditions including diabetes-associated vascular complications, cardiovascular disorders (CVDs), pulmonary diseases, cancers, and others. This chapter describes the basic mechanism through which RAGE fuels the inflammatory and oxidative stress on a cellular front.