Mechanisms of disease: the oxidative stress theory of diabetic neuropathy.
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.
Figueroa-Romero
Claudia
C
Department of Neurology, University of Michigan, 5017 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.
Sadidi
Mahdieh
M
Feldman
Eva L
EL
D000818:Animals; D003929:Diabetic Neuropathies / Q000209:etiology*; D005947:Glucose; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006595:Hexosamines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D053858:Metabolic Networks and Pathways; D051336:Mitochondrial Membranes / Q000378:metabolism; D023421:Models, Animal; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013402:Sugar Alcohols / Q000378:metabolism
D017127:Glycation End Products, Advanced; D006595:Hexosamines; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013402:Sugar Alcohols; D011065:Poly(ADP-ribose) Polymerases; D011493:Protein Kinase C; D005947:Glucose