Advanced glycation endproducts or advanced glycation end products (AGEs) levels increase in blood or tissue during aging and in diseases such as diabetes and renal failure. The receptor of advanced glycation endproducts (RAGE), is a multi-ligand receptor belonging to the immunoglobulin superfamily. It is weakly expressed in most adult tissues. The link between the RAGE and its ligands triggers a cascade of intracellular events, followed by the transcription of a range of genes involved in different biological systems, as well as other reactions such as the formation of oxidative stress. All of these reactions lead to a series of functional changes that participate in neurological and vascular complications of diabetes, metabolic syndrome. They are also involved in Alzheimer's disease, arthritis, and some cancers. Besides the presence of these ligands, the chronic stimulation of the RAGE, or its isoforms trigger different signaling pathways and reactions. This makes complex the analysis of biological networks associated with multiple clinical traits. Many issues remain to be clarified in the pathogenicity of RAGE. In the era of the development of systems biology, integrative approach is expected allowing a better understanding of the overall effects of RAGE system. In this review, we discuss recent advances in our understanding of the biology of the RAGE, focusing on how systems biology influence our view it processes. The review should contribute to the better understanding of pathogenicity of "RAGE system" and to the transposition this new knowledge into clinical and translational research.
Keywords: AGEs; RAGE receptor; biological network; glycation; systems biology.