The Nrf2-Antioxidant Response Element Signaling Pathway and Its Activation by Oxidative Stress*

By Truyen Nguyen, P. Nioi, C. B. Pickett. Journal of Biological Chemistry, 2009

2,520 citations recorded by the source corpus.

A major mechanism in the cellular defense against oxidative or electrophilic stress is activation of the Nrf2-antioxidant response element signaling pathway, which controls the expression of genes whose protein products are involved in the detoxication and elimination of reactive oxidants and electrophilic agents through conjugative reactions and by enhancing cellular antioxidant capacity. At the molecular level, however, the regulatory mechanisms involved in mediating Nrf2 activation are not fully understood. It is well established that Nrf2 activity is controlled, in part, by the cytosolic protein Keap1, but the nature of this pathway and the mechanisms by which Keap1 acts to repress Nrf2 activity remain to be fully characterized and are the topics of discussion in this minireview. In addition, a possible role of the Nrf2-antioxidant response element transcriptional pathway in neuroprotection will also be discussed.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/8d706ae38f9d1d6333a521bb9036bd42a29142d9

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In Molecular Biology

1. D. Tuveson
2. I. I. C. Chio
3. C. Tonelli

Citations in the corpus

• The eIF2α kinases: their structures and functions (2013, neutral): “Under normal conditions, it is constitutively degraded in a KEAP1-dependent manner (see [137] for a recent review on NRF2 regulation).”
• Role of Glutathione in Cancer Progression and Chemoresistance (2013, background): “These substances are electrophiles and form conjugates with GSH, either spontaneously or enzymatically, in reactions catalyzed by GSH-S-transferases (GST) [22].”
• Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders (2010, neutral): “Whereas many aspects of the model are still controversial and the intricate details of the regulation of the pathway are not fully understood (200, 324, 345), there is voluminous experimental evidence for a mechanism of regulation of Keap1 activity through its reactive cysteine residues.”
• Transcriptional Regulation by Nrf2 (2017, background): “In response to different activating stimuli, Nrf2 is stabilized and translocates to the nucleus, where it activates the transcription of its downstream targets (49, 117).”
• Oxidative stress in ALS: key role in motor neuron injury and therapeutic target. (2010, neutral): “2) [72].”
• Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis (2011, neutral): “(3) 5′-CAUGUUACGUGAUGAGGAU-3′ (4) 5′-GGACAGCAAUUACCAUUUU-3′”