Abstract
Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes mellitus and the leading cause of end stage renal disease. One of the key pathways activated in DN is the polyol pathway, in which glucose is converted to sorbitol (a relatively nonmetabolizable sugar) by the enzyme aldose reductase (AR). Shunting of glucose into this pathway causes disruption to glucose metabolism and subsequently damages the tissues via increased oxidative stress, protein kinase c activation and production of advanced glycation end products (AGE) in the kidney. This review aims to provide a comprehensive overview of the AR enzyme structure, substrate specificity and topology in normal physiology; to elaborate on the deleterious effects of AR activation in DN; and to summarize the potential therapeutic benefits and major challenges associated with AR inhibition in patients with DN.
Keywords: Diabetic nephropathy, aldose reductase, polyol pathway, protein kinase C, sorbitol, oxidative stress, advanced glycation end products.
Graphical Abstract
Protein & Peptide Letters
Title:Aldose Reductase as a Drug Target for Treatment of Diabetic Nephropathy: Promises and Challenges
Volume: 24 Issue: 1
Author(s): Heba El Gamal and Shankar Munusamy
Affiliation:
Keywords: Diabetic nephropathy, aldose reductase, polyol pathway, protein kinase C, sorbitol, oxidative stress, advanced glycation end products.
Abstract: Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes mellitus and the leading cause of end stage renal disease. One of the key pathways activated in DN is the polyol pathway, in which glucose is converted to sorbitol (a relatively nonmetabolizable sugar) by the enzyme aldose reductase (AR). Shunting of glucose into this pathway causes disruption to glucose metabolism and subsequently damages the tissues via increased oxidative stress, protein kinase c activation and production of advanced glycation end products (AGE) in the kidney. This review aims to provide a comprehensive overview of the AR enzyme structure, substrate specificity and topology in normal physiology; to elaborate on the deleterious effects of AR activation in DN; and to summarize the potential therapeutic benefits and major challenges associated with AR inhibition in patients with DN.
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Cite this article as:
Gamal El Heba and Munusamy Shankar, Aldose Reductase as a Drug Target for Treatment of Diabetic Nephropathy: Promises and Challenges, Protein & Peptide Letters 2017; 24 (1) . https://dx.doi.org/10.2174/0929866523666161128153548
DOI https://dx.doi.org/10.2174/0929866523666161128153548 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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