Title: Biochemical process of AGEs formation in complications of hyperglycemia-induced diabetes and its pathological damage effects: A possible target for new drugs
Abstract:Advanced glycation end-products (AGEs) are closely related to diabetes mellitus and complications of diabetes. This article reviews the biochemical process of AGEs formation, its structure, function, ...Advanced glycation end-products (AGEs) are closely related to diabetes mellitus and complications of diabetes. This article reviews the biochemical process of AGEs formation, its structure, function, and pathological effects on complications of hyperglycemia-induced diabetes, such as cardiovascular complications, retinopathy, neuropathy and nephropathy. Reducing sugars react non-enzymatically with ami no groups in proteins through Maillard reaction by forming Schiff bases and Amadori products to produce AGEs irreversibly. The pathological crosslink formation induced by AGEs leads to increased stiffness of protein matrix, which will cause sclerosis of renal glomerulus, thickening of the capillary basement membrane and development of arteriosclerosis. Receptor for AGEs (RAGE) , a multiligand member of immunoglobulin su-perfamily, acts as an AGEs scavenger and mediates intracellular signaling. Although the mechanism of how AGEs cause hyperglycemia-induced diabetic complications is not fully understood, three possible pathways have been proposed: (1) the cross-link of AGEs and proteins; (2) the interaction of AGE-RAGE and cellular biosignal transduction; (3) oxidative stress. Nowadays there are at least three strategies of treatments aiming at AGEs. Firstly, therapeutic interventions for reducing AGEs formation should stress the AGEs formation by reducing cross-link formation. The second strategy is a reduction in AGEs deposition, which might be achieved by using cross-link breakers or by enhancing cellular uptake and degradation. The third is inhibition of AGEs receptor by using neutralizing antibodies, or suppression of post-receptor signaling by using antioxi-dants. All these provide a new conceptual framework for future drug discovery.Read More
Publication Year: 2003
Publication Date: 2003-01-01
Language: en
Type: article
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