Description
Advanced glycation end products (AGEs) are important biochemical compounds found in diabetes and may be associated with inflammatory processes. In the vessel wall, AGEs are bound to specific receptors to modulate many cellular properties by activating several signaling pathways. One of these receptors is called "Receptor for Advanced Glycation End product" (RAGE). RAGE is a multi-ligand member of the immunoglobulin superfamily of cell surface molecules that is expressed in a variety of cell lines, including endothelial cells, smooth muscle cells, mononuclear phagocytes, pericytes, neurons, cardiac myocytes, mesangial cells and hepatocytes. RAGE interacts with different structures to transmit a signal into the cell and recognizes three-dimensional structures rather than specific amino acid sequences. Therefore, RAGE seems to fulfill the requirements of a pattern-recognition receptor. As a member of the immunoglobulin superfamily, it interacts with a diverse class of ligands, including AGEs, HMGB1 (also known as Amphoterin), amyloid β-peptide, amyloid A, leukocyte adhesion receptors, prions, Escherichia coli curli operons, β-sheet fibrils and several members of the S100 protein superfamily including S100/calgranulins. Thus RAGE may have potential involvement in several pathological processes
including inflammation, diabetes, Alzheimer's disease (AD), systemic amyloidosis and tumor growth. AGE-RAGE interaction enhances the expression of genes encoding cytokines, growth factors and adhesion molecules, and increases the classical acute phase proteins. Potential approaches to prevention and treatment of diabetes and its complications include inhibition of AGE formation, breakage of preformed AGE-proteins crosslink, blockade of AGE-RAGE interactions with RAGE competitors, antibody antagonists and RAGE specific metabolic inhibition. Inhibition of AGE-RAGE complex formation is able to suppress the levels of pro-inflammatory cytokines and growth factors and may be considered as a target for overcoming diabetic complications