Role of advanced glycation end products and their receptors in development of diabetic neuropathy.
Diabetic neuropathy is a life-threatening complication involving both peripheral and autonomic nerves. The hyperglycemia-induced polyol pathway as well as enhanced oxidative stress are among the factors implicated in the pathogenesis of diabetic neuropathy. Their effects are possibly exerted by direct nerve tissue damage or mediated by endothelial injury or vascular dysfunction. Formation of advanced glycation end product (AGE) is another important candidate for the cause of peripheral neuropathy. Indeed, the levels of AGEs were increased in the serum and also in the peripheral nerves obtained from diabetic patients. Structural and functional proteins of those nerves are also glycated, resulting in impaired nerve function and characteristic pathologic alterations. In addition, interaction between AGEs and their receptors induce biological effects on the target tissues for diabetic complications. In the peripheral nerve, the receptor for AGE (RAGE) is expressed in endothelial and Schwann cells. It is thus anticipated that interactions between AGEs and RAGE facilitate endoneural vascular dysfunction, leading to microangiopathy in the peripheral nerve. The roles of these mechanisms, in particular on the molecular mechanisms of AGE-RAGE interactions in the development of diabetic neuropathy are largely still speculative and yet to be explored.
Wada
Ryuichi
R
Department of Pathology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562 Japan. ryuichi@cc.hirosaki-u.ac.jp
Yagihashi
Soroku
S
D000818:Animals; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D018450:Disease Progression; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D017933:Peripheral Nervous System / Q000503:physiopathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic