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

Mehrdad Hashemi, Mohammad Arad Zandieh, Setayesh Ziaolhagh, Sarah Mojtabavi, Farzaneh Hasani Sadi, Zeinab Khazaei Koohpar, Maryam Ghanbarirad, Arvin Haghighatfard, Mitra Behroozaghdam, Ramin Khorrami, Noushin Nabavi, Jun Ren, Russel J. Reiter, Shokooh Salimimoghadam, Mohsen Rashidi, Kiavash Hushmandi, Afshin Taheriazam, Maliheh Entezari

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations


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.

Original languageEnglish (US)
Article number166714
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number5
StatePublished - Jun 2023


  • Diabetes mellitus
  • Diabetic cardiomyopathy
  • Diabetic nephropathy
  • Diabetic neuropathy
  • Kidney dysfunction
  • Nuclear factor erythroid 2-related factor 2

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology


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