Keap1/Nrf2/ARE signaling unfolds therapeutic targets for redox imbalanced-mediated diseases and diabetic nephropathy.

Hyperglycemia/oxidative stress has been implicated in the initiation and progression of diabetic complications while the components of Keap1/Nrf2/ARE signaling are being exploited as therapeutic targets for the treatment/management of these pathologies. Antioxidant agents like drugs, nutraceuticals and pure compounds that target the proteins of this pathway and their downstream genes hold the therapeutic strength to put the progression of this disease at bay. Here, we elucidate how the modulation of Keap1/Nrf2/ARE had been exploited for the treatment/management of end-stage diabetic kidney complication (diabetic nephropathy) by looking into (1) Nrf2 nuclear translocation and phosphorylation by some protein kinases at specific amino acid sequences and (2) Keap1 downregulation/Keap1-Nrf2 protein-protein inhibition (PPI) as potential therapeutic mechanisms exploited by Nrf2 activators for the modulation of diabetic nephropathy biomarkers (Collagen IV, Laminin, TGF-β1 and Fibronectin) that ultimately lead to the amelioration of this disease progression. Furthermore, we brought to limelight the relationship between diabetic nephropathy and Keap1/Nrf2/ARE and finally elucidate how the modulation of this signaling pathway could be further explored to create novel therapeutic milestones.