Abstract
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 tissuespecific 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.
Keywords: Cyclooxygenase-2, diabetes, diabetic peripheral neuropathy, oxidative stress, prostaglandins, inflammation
Current Drug Targets
Title: Cyclooxygenase-2 Pathway as a Potential Therapeutic Target in Diabetic Peripheral Neuropathy
Volume: 9 Issue: 1
Author(s): Rodica Pop-Busui, Aaron P. Kellogg and Hsinlin Thomas Cheng
Affiliation:
Keywords: Cyclooxygenase-2, diabetes, diabetic peripheral neuropathy, oxidative stress, prostaglandins, inflammation
Abstract: 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 tissuespecific 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.
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Cite this article as:
Pop-Busui Rodica, Kellogg P. Aaron and Cheng Thomas Hsinlin, Cyclooxygenase-2 Pathway as a Potential Therapeutic Target in Diabetic Peripheral Neuropathy, Current Drug Targets 2008; 9 (1) . https://dx.doi.org/10.2174/138945008783431691
DOI https://dx.doi.org/10.2174/138945008783431691 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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