Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the endogenous antioxidant response to reactive oxygen species as well as a controller of Phase II detoxification in response to xenobiotics. This amenity to specific external manipulation exploits the binding affinity of Nrf2 for its constitutive repressor and degradation facilitator Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1). Derived from both natural and synthesized origins, these compounds have been extensively tested without definitive beneficial results. Unfortunately, multiple terminated trials have shown a negative side to Nrf2 with regard to cardiac pathologies while animal-based studies have demonstrated cardiomyocyte hypertrophy and heart failure after chronic Nrf2 upregulation. Putatively based on autophagic control of Nrf2 activity-modulating upstream factors, new evidence of miRNA involvement has added complexity to this mechanism. What follows is an extensive survey of Nrf2-regulating exogenous compounds that may promote cardiomyopathy, clinical trial evidence, and a comparison to exercise-induced factors that also upregulate Nrf2 while preventing cardiac pathologies.
Reference141 articles.
1. Stress-Activated Cap’n’collar Transcription Factors in Aging and Human Disease;Sykiotis;Sci. Signal.,2010
2. Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases;Cuadrado;Nat. Rev. Drug Discov.,2019
3. He, F., Ru, X., and Wen, T. (2020). NRF2, a Transcription Factor for Stress Response and Beyond. Int. J. Mol. Sci., 21.
4. Mathis, B.J., and Cui, T. (2020). Nrf2 and its Modulation in Inflammation, Springer. Progress in Inflammation Research.
5. Redox-regulated Turnover of Nrf2 Is Determined by at Least Two Separate Protein Domains, the Redox-sensitive Neh2 Degron and the Redox-insensitive Neh6 Degron;McMahon;J. Biol. Chem.,2004
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