Chemical and Biological Mechanisms of Phytochemical Activation of Nrf2 and Importance in Disease Prevention

Overview

Journal Recent Adv Phytochem

Specialty Chemistry

Date 2016 Feb 9

PMID 26855455

Citations 18

Authors

Aimee L Eggler

Sergey N Savinov

Affiliations

Soon will be listed here.

Abstract

Plants are an incredibly rich source of compounds that activate the Nrf2 transcription factor, leading to upregulation of a battery of cytoprotective genes. This perspective surveys established and proposed molecular mechanisms of Nrf2 activation by phytochemicals with a special emphasis on a common chemical property of Nrf2 activators: the ability as "soft" electrophiles to modify cellular thiols, either directly or as oxidized biotransformants. In addition, the role of reactive oxygen/nitrogen species as secondary messengers in Nrf2 activation is discussed. While the uniquely reactive C151 of Keap1, an Nrf2 repressor protein, is highlighted as a key target of cytoprotective phytochemicals, also reviewed are other stress-responsive proteins, including kinases, which play non-redundant roles in the activation of Nrf2 by plant-derived agents. Finally, the perspective presents two key factors accounting for the enhanced therapeutic windows of effective phytochemical activators of the Keap1-Nrf2 axis: enhanced selectivity toward sensor cysteines and reversibility of addition to thiolate molecules.

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