title: Aldose Reductase as a Drug Target for Treatment of Diabetic Nephropathy: Promises and Challenges.
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.
authors.forename: Heba
authors.initials: H
authors.lastname: ElGamal
authors.affiliation: College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar.
authors.forename: Shankar
authors.initials: S
authors.lastname: Munusamy
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D020134:Catalytic Domain; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013012:Sorbitol / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D013012:Sorbitol; D000449:Aldehyde Reductase; D005947:Glucose
keywords: Diabetic nephropathy; advanced glycation
  end products; aldose reductase; oxidative stress; polyol pathway; protein kinase C; sorbitol