Targeting the KEAP1-NRF2 System to Prevent Kidney Disease Progression

BACKGROUND: Nuclear factor erythroid 2-related factor 2 (NRF2) is a critical transcription factor for the antioxidative stress response and it activates a variety of cytoprotective genes related to redox and detoxification. NRF2 activity is regulated by the oxidative-stress sensor molecule Kelch-like ECH-associated protein 1 (KEAP1) that induces proteasomal degradation of NRF2 through ubiquitinating NRF2 under unstressed conditions. Because oxidative stress is a major pathogenic and aggravating factor for kidney diseases, the KEAP1-NRF2 system has been proposed to be a therapeutic target for renal protection. SUMMARY: Oxidative-stress molecules, such as reactive oxygen species, accumulate in the kidneys of…