Abstract
The redox-sensitive signaling system Keap1/Nrf2/ARE plays a key role in maintenance of cellular homeostasis under stress, inflammatory, carcinogenic, and proapoptotic conditions, which allows us to consider it as a pharmacological target. Here we review the basic regulatory mechanisms of the Keap1/Nrf2/ARE system, key targets for pharmacological intervention, and interconnection of this system with other redox-sensitive transcriptional factors. We also discuss the range of currently available pharmaceuticals. Finally, we promote “indirect” antioxidants as a promising strategy for prevention and treatment of wide range of diseases associated with oxidative stress.
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Abbreviations
- ARE:
-
antioxidant-responsive element
- CNC:
-
cap’n’Collar family
- Cul3-E3-ligase:
-
Cullin-3-containing ubiquitin-ligase complex E3
- Keap1:
-
Kelch-like ECH-associated protein 1
- MAPK:
-
mitogen-activated protein kinases
- NQO1:
-
NAD(P)H:quinone oxidoreductase 1
- Nrf2:
-
NF-E2-bound factor 2
- ROS:
-
reactive oxygen species
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Original Russian Text © N. K. Zenkov, E. B. Menshchikova, V. O. Tkachev, 2013, published in Biokhimiya, 2013, Vol. 78, No. 1, pp. 27–47.
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Zenkov, N.K., Menshchikova, E.B. & Tkachev, V.O. Keap1/Nrf2/ARE redox-sensitive signaling system as a pharmacological target. Biochemistry Moscow 78, 19–36 (2013). https://doi.org/10.1134/S0006297913010033
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DOI: https://doi.org/10.1134/S0006297913010033