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Mechanisms of disease: The oxidative stress theory of diabetic neuropathy

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Abstract

Diabetic neuropathy is the most common complication of diabetes, affecting 50% of diabetic patients. Currently, the only treatment for diabetic neuropathy is glucose control and careful foot care. In this review, we discuss the idea that excess glucose overloads the electron transport chain, leading to the production of superoxides and subsequent mitochondrial and cytosolic oxidative stress. Defects in metabolic and vascular pathways intersect with oxidative stress to produce the onset and progression of nerve injury present in diabetic neuropathy. These pathways include the production of advanced glycation end products, alterations in the sorbitol, hexosamine and protein kinase C pathways and activation of poly-ADP ribose polymerase. New bioinformatics approaches can augment current research and lead to new discoveries to understand the pathogenesis of diabetic neuropathy and to identify more effective molecular therapeutic targets.

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Acknowledgements

We thank Ms. Judith Boldt for excellent secretarial support and Dr. Kelli A. Sullivan for expert editorial advice. This work was supported by the A. Alfred Taubman Medical Research Institute, the Program for Neurology Research and Discovery and by NIH T32 NS07222 and NIH UO1 DK076160.

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Correspondence to Eva L. Feldman.

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Figueroa-Romero, C., Sadidi, M. & Feldman, E.L. Mechanisms of disease: The oxidative stress theory of diabetic neuropathy. Rev Endocr Metab Disord 9, 301–314 (2008). https://doi.org/10.1007/s11154-008-9104-2

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