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:College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar.
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.
