RAGE: The Beneficial and Deleterious Effects by Diverse Mechanisms of Actions

Receptor for advanced glycation endproducts (RAGE) is a transmembrane protein that belongs to the immunoglobu-lin superfamily. RAGE is expressed ubiquitously-high in lung and moderate to low in a wide range of cells-in a tightly regulated manner at various stages of development. RAGE is a pattern recognition receptor that binds to multi-ple ligands, including amphoterin, members of the S100/ calgranulin family, the integrin Mac-1, and amyloid β-pep-tide (Aβ). RAGE-ligand engagement effects the activation of diverse cascades that initiate and stimulate chronic stress pathways and repair, depending on the ligand, envi-ronment, and developmental stage. Further, RAGE-ligand interaction and the consequent upregulation of RAGE through a positive feedback loop are often associated with various diseases, including vascular disease, diabetes, cancer, and neurodegenerative disease. It is unknown how RAGE mediates these events, but such phenomena ap-pear to be linked to the inflammatory response. In this review, we summarize the findings on RAGE from pub-lished reports and ongoing studies. Also, the implication of RAGE in Alzheimer disease, the most common neuro-degenerative disease in the elderly population, will be dis-cussed, with a focus on Aβ-RAGE interactions with regard to signaling pathways and their impact on cellular activity.