Mediation pathways for the receptor for advanced glycation end products in diabetic nephropathy

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Excess sugar in the blood from diabetes is detrimental and can accelerate a process where sugar attaches itself to proteins, fats and DNA. Although facilitated by high sugar, the reaction occurs happily in the presence of low sugar with high levels of free oxygen radicals. These complexes are called advanced glycation end products or AGEs. In addition, we ingest vast volumes of AGES from our diet which are taken into the blood. These AGEs are known to be involved in the development of kidney disease in diabetic subjects. AGEs exert most of their effects on the body by binding to specific proteins, the most common and nasty of which is the receptor for advanced glycation end products, RAGE. RAGE is a known participant in other serious diseases such as Alzheimer's disease and evidence is mounting for its central role in the development of kidney disease in diabetic subjects. There is not much known about the processes which mediate RAGE which is why this is the aim of this proposal. This will enable us to stop the relentless progression of kidney disease in diabetes.