The Receptor for Advanced Glycation End Products: Regulation and Implications in Metabolic Diseases.

Receptor for advanced glycation end-products (RAGE) was originally identified as a receptor for advanced glycation end-products; however, it can also bind a broader range of damage-associated molecular patterns, including S100 proteins, high mobility group box 1, and amyloid-β. Ligand-induced RAGE activation promotes receptor oligomerization and recruitment of diaphanous-related formin-1, which activates several intracellular cascades, leading to the production of inflammatory mediators and reactive oxygen species. RAGE expression is upregulated in disease-associated tissues, including adipose tissue in diabetes and microglia and neurons in Alzheimer's disease, and the mechanisms by which RAGE activation contributes to pathogenesis are disease-specific. The review summarizes the expression and activation of RAGE, and the potential mechanisms through which RAGE contributes to disease pathogenesis. We further discuss current and emerging strategies for modulating RAGE signaling and highlight their therapeutic potential in the prevention and treatment of RAGE-associated diseases.