Oxidative stress and Nrf2 in the pathophysiology of diabetic neuropathy: Old perspective with a new angle

Long-standing diabetes and complications thereof particularly, neuropathy stands for one of the major causes of morbidity across the globe. It is postulated that excessive production of reactive oxygen species is a key component in the development and progression of diabetic neuropathy. Oxidative damage is the most common concluding pathway for various pathogenetic mechanisms of neuronal injury in diabetic neuropathy. However despite optimistic preclinical data, it is still very ambiguous that why antioxidants have failed to demonstrate significant neuroprotection in humans. A growing body of evidences now suggests that strategies utilizing a more targeted approach like focusing on Nrf2 (a transcription factor modulating oxidative stress) may provide an enthralling avenue to optimize neuroprotection in diabetes and diabetic neuropathy. This review presents an emerging concept of Nrf2 in diabetic neuropathy; thus looking forward to newer strategies for combating the oxidant induced damage.

► Oxidative stress plays a major role in the pathophysiology of diabetic neuropathy.
► Nrf2 is key transcription factor maintaining the antioxidant defense.
► Nrf2 has gained value due to its role in neuroprotection, inflammation and cancer.
► Nrf-2 activators hold a potential for protection of diabetic peripheral nerves.