Therapeutic Approach on AGE-RAGE Interaction and Its Function in Diabetic Inflammation Process
Clara A. Veloso, Caroline M.O. Volpe, Cristina L. Carrara, Miriam M. Chaves and Jose A. Nogueira-Machado
Affiliation: Nucleo de Pos Graduacao e Pesquisa (NPGP), Hospital Santa Casa de Misericordia de Belo Horizonte -Belo Horizonte - MG-Brasil.
Keywords: Diabetes, AGEs, RAGE, inflammation, cytokines, patents, diacylglycerol-protein kinase C, DAG-PKC pathway, Amadori's product, carboximethyl lysine, CML, fluorescent cross-linking species, non-fluorescent and non-cross linking species, antioxidant compounds, aminosalicyclic acid, N-acetylcysteine, lipoic acid amide, para-aminobenzoic acid, inositol, probucol, synthetic AGE inhibitors, aminoguanidine, hydrazono-oxo-thiazolidine derivatives, aspirin, pyridoxamine, ibuprofen, indo-methacin, pentoxifylline, benfotiamine, amadorins, N-phenacylthiazolium-bromide, pyridazinone derivative, thiourea, phenylguanidine, arylcarboxilic acid, chondroitin sulfate, homopiperazine derivative, chalcone derivative, arylpropane derivative, phenylpropeneamid derivative
Advanced glycation end products (AGEs) are important biochemical compounds found in diabetes mellitus and are likely to be associated with an inflammatory process. Within the vessel wall, AGEs may interact with specific receptors to modulate a large number of cellular properties by activating several signaling pathways. One of these receptors is called “receptor for AGE” (RAGE). The AGE-RAGE interactions enhance transcription genes encoding for cytokines, growth factors, adhesive molecules and increased classical acute phase proteins. Potential preventive and therapeutic approaches toward 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. Blockade of AGE-RAGE complex formation suppresses the levels of pro-inflammatory cytokines and growth factors and it may be considered as a target for overcoming diabetic complications. This concise review about AGE-RAGE interaction and diabetes complications discusses pathophysiological mechanisms at a glance. Patents on inhibition of AGE formation, RAGE expression and AGE-RAGE interaction are shown and discussed here.
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