Les produits de fin de glycation des protéines (AGEs) et leur récepteur en pathologie

Advanced glycated end products (AGEs) are produced following the biochemical reaction of a protein with a sugar referred to as the « Maillard reaction ». Because of increased glycemia in pathological conditions such as type 1 and type 2 diabetes, AGEs accumulate in tissues, bind along other ligands to their receptor RAGE and initiate signaling pathways that increase oxidative stress and induce the expression of genes involved in inflammatory cell recruitment and cell surface increased expression of RAGE. One of the key players is the transcription factor nuclear factor kappa B (NFκB), which participate in the sustained RAGE-mediated inflammatory response. These biological processes induce further accumulation of AGEs, other RAGE ligands (HMGB1, S100/calgranulins, MAC-1), and reactive oxygen species which contribute to the several complications of diabetes. Soluble forms of RAGE, sRAGE and an alternate splicing form RAGE_v1 or esRAGE, are thought to mitigate the effects of AGEs by favouring their clearance and therefore prevent their deleterious effects. RAGE and its ligands accumulate also in conditions other than diabetes such as cancer and cardiovascular pathologies. In this report, we review the principle actions of AGEs and RAGE in human disease. Development of RAGE antagonists might help reduce the burden of several complications of diabetes and other pathological conditions such as cancer and inflammatory diseases.