Cyclooxygenase-2 pathway as a potential therapeutic target in diabetic peripheral neuropathy.
Diabetic peripheral neuropathy (DPN) is the most common diabetic complication and is the leading cause of diabetes-related hospital admissions and non-traumatic amputations. DPN is also associated with a poor quality of life and high economic costs for both type 1 and type 2 diabetic patients. An effective treatment for DPN, besides tight glycemic control, is not yet available. The pathogenesis of DPN is complex and involves an intertwined array of mechanisms. Glucose-mediated alteration of cyclooxygenase (COX) pathway activity with subsequent impaired production and function of prostaglandins (PGs) is one mechanism that is implicated in the pathogenesis of DPN. COX-2, the inducible COX isoform, is upregulated in a variety of pathophysiological conditions including diabetes. COX-2 upregulation has tissue-specific consequences and is associated with activation of downstream inflammatory reactions. We have previously reported that COX-2 is upregulated in the peripheral nerves and dorsal root ganglia neurons in experimental diabetes and that COX-2 gene inactivation and/or selective COX-2 inhibition provides protection against various DPN deficits. This review will summarize current evidence supporting the role of COX-2 activation in inducing diabetic neurovascular dysfunction and that modulation of the COX-2 pathway is a potential therapeutic target for DPN.
Kellogg
Aaron P
AP
Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, USA.
Cheng
Hsinlin Thomas
HT
Pop-Busui
Rodica
R
D000818:Animals; D051546:Cyclooxygenase 2 / Q000187:drug effects* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D016503:Drug Delivery Systems; D006801:Humans; D018384:Oxidative Stress; D015854:Up-Regulation
D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2