Nrf2 signaling in diabetic nephropathy, cardiomyopathy and neuropathy: Therapeutic targeting, challenges and future prospective

Western lifestyle contributes to an overt increase in the prevalence of metabolic anomalies including diabetes mellitus (DM) and obesity. Prevalence of DM is rapidly growing worldwide, affecting many individuals in both developing and developed countries. DM is correlated with the onset and development of complications with diabetic nephropathy (DN), diabetic cardiomyopathy (DC) and diabetic neuropathy being the most devastating pathological events. On the other hand, Nrf2 is a regulator for redox balance in cells and accounts for activation of antioxidant enzymes. Dysregulation of Nrf2 signaling has been shown in various human diseases such as DM. This review focuses on the role Nrf2 signaling in major diabetic complications and targeting Nrf2 for treatment of this disease. These three complications share similarities including the presence of oxidative stress, inflammation and fibrosis. Onset and development of fibrosis impairs organ function, while oxidative stress and inflammation can evoke damage to cells. Activation of Nrf2 signaling significantly dampens inflammation and oxidative damage, and is beneficial in retarding interstitial fibrosis in diabetic complications. SIRT1 and AMPK are among the predominant pathways to upregulate Nrf2 expression in the amelioration of DN, DC and diabetic neuropathy. Moreover, certain therapeutic agents such as resveratrol and curcumin, among others, have been employed in promoting Nrf2 expression to upregulate HO-1 and other antioxidant enzymes in the combat of oxidative stress in the face of DM.

Automated summary

The Western lifestyle has led to an increase in metabolic anomalies such as diabetes mellitus (DM) and obesity. DM has rapidly grown worldwide, affecting individuals in both developing and developed countries, and is associated with complications like diabetic nephropathy (DN), diabetic cardiomyopathy (DC), and diabetic neuropathy. Dysregulation of Nrf2 signaling, which regulates cellular redox balance and activates antioxidant enzymes, has been observed in DM and other human diseases. This review discusses the role of Nrf2 signaling in major diabetic complications and the potential of targeting Nrf2 for treatment. These complications share similarities including oxidative stress, inflammation, and fibrosis and activating Nrf2 signaling can help reduce inflammation, oxidative damage, and interstitial fibrosis in diabetic complications. Pathways like SIRT1 and AMPK can upregulate Nrf2 expression in the amelioration of DN, DC, and diabetic neuropathy. Additionally, therapeutic agents like resveratrol and curcumin have been used to promote Nrf2 expression and combat oxidative stress in DM.