Therapeutic interruption of advanced glycation in diabetic nephropathy: do all roads lead to Rome?
A major common feature of the chemically disparate compounds that inhibit advanced glycation end product (AGE) accumulation or signaling is their ability to show end-organ protection in experimental models of diabetes complications. The mechanisms by which these AGE- lowering therapies confer their benefits remain unsolved. Is it the reduction in tissue AGE levels per se or the inhibition of downstream signal transduction (as has been described with the soluble receptor for AGE)? Possible modes of action that need to be investigated include the ability of some of these agents to stimulate antioxidant defenses, to lower cholesterol and other lipid levels, and to inhibit low-grade inflammation. To understand these novel mechanisms, further examination of the advanced glycation pathway and, in particular, the diverse action of these agents in ameliorating the development of diabetic complications is needed.
Sourris
Karly C
KC
JDRF Albert Einstein Centre for Diabetes Complications, Diabetes and Metabolism Division, Baker Heart Research Institute, Melbourne, Victoria, Australia.
Forbes
Josephine M
JM
Cooper
Mark E
ME
D002336:Carnosine / Q000627:therapeutic use; D048909:Diabetes Complications / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D006801:Humans; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D013844:Thiazoles / Q000627:therapeutic use
D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D013844:Thiazoles; D002336:Carnosine; C406794:alagebrium