REVIEW: Keap1/Nrf2/ARE Redox-Sensitive Signaling System as a Pharmacological Target

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N. K. Zenkov¹, E. B. Menshchikova^1*, and V. O. Tkachev^1,2

¹Scientific Center of Clinical and Experimental Medicine, Siberian Branch of the Russian Academy of Medical Sciences, ul. Timakova 2, 630117 Novosibirsk, Russia; fax: (383) 333-6456; E-mail: lemen@soramn.ru

²Current address: University of Michigan School of Medicine, 1301 Catherine Road, Ann Arbor, MI 48109, USA, E-mail: vtkachev@med.umich.edu

^* To whom correspondence should be addressed.

Received July 4, 2012; Revision received September 4, 2012

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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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KEY WORDS: Nrf2, antioxidant-responsive element (ARE), transcription factors, pharmaceuticals

DOI: 10.1134/S0006297913010033

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