RESUMO
The receptor for advanced glycation end-product (RAGE) is the signal transduction receptor which senses a variety of signalling molecules including advanced glycation end products (AGEs), HMGB1, S100/calgranulins, ß-amyloid, phosphatidylserine, C3a and advanced oxidation protein products (AOPPs). It is usually abnormally up-regulated and plays crucial roles during the development of many human diseases such as diabetes, cardiovascular diseases, osteoarthritis and cancer. RAGE regulates a number of cell processes of pivotal importance like inflammation, apoptosis, proliferation and autophagy. Therapeutic strategies to block RAGE may represent great therapeutic potentials and therefore it has been under extensive investigation during the last decade. Accordingly, there is a growing interest of unraveling the intracellular signalling pathways by which RAGE controls these disease-related processes. Early studies are mainly focused on inflammatory pathways involving the NFκB and the MAPK pathways. Nevertheless, many novel signalling pathways implicated in other cell processes, such as autophagy, have also recently been found to be activated upon RAGE stimulation and contribute to the detrimental effects of RAGE. In this review, we aim to provide a comprehensive summary of previous and recent studies relating to the complex molecular network of RAGE signalling, with a particular emphasis on RAGE transgenic mouse models.
Assuntos
Produtos Finais de Glicação Avançada/metabolismo , Receptores Imunológicos/genética , Transdução de Sinais/genética , Animais , Movimento Celular , Proliferação de Células , Sobrevivência Celular , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica , Humanos , Inflamação/genética , Inflamação/metabolismo , Camundongos , Camundongos Transgênicos , NF-kappa B/genética , NF-kappa B/metabolismo , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/metabolismoRESUMO
The modification of free amino groups on proteins, lipids, and nucleic acids by non-enzymatic glycosylation produce a variety of complex structures named advanced glycation end products (AGEs). Glycation of these molecules participate in the development of diabetic complications and related diseases. Diabetes mellitus is characterized by short-term metabolic changes in lipid and protein metabolism, and long-term irreversible changes in vascular and connective tissue. AGEs are directly implicated in the development of chronic complications in diabetes such as nephropathy, rethinopathy, neuropathy, and other related diseases such as atherosclerosis, heart disease, stroke, and peripheral vascular disease. In this review, we aim to explain how glycation occurs in different molecules and what the pathological consequence of AGE formation in diabetes mellitus and other diseases are.
Assuntos
Diabetes Mellitus/metabolismo , Glucose/metabolismo , Complicações do Diabetes/metabolismo , HumanosRESUMO
Advanced glycation end-products (AGEs) are heterogeneous groups of compounds that result from the non-enzymatic reaction of reducing sugars with free amino groups of biological molecules such as proteins, lipids, and nucleic acids. A large number of studies have been focused on AGEs metabolism, analysis, treatments, and their implications in the pathogenesis of diseases, especially in diabetes mellitus. Here, we review recent advances in the understanding of pathological complications caused by the production of AGEs. We provide an overview of the most important issues published within this area in last years; we also present the number of scientific papers related to AGEs available since 1950 until 2008 in the most important fields including metabolism, physiology, and pharmacology, thus as analytical methods for AGE detection and quantification and studies carried out in human body fluids. Data were collected from ovidSP.