Nrf2-ARE stress response mechanism: a control point in oxidative stress-mediated dysfunctions and chronic inflammatory diseases.
Nrf2, a redox sensitive transcription factor, plays a pivotal role in redox homeostasis during oxidative stress. Nrf2 is sequestered in cytosol by an inhibitory protein Keap1 which causes its proteasomal degradation. In response to electrophilic and oxidative stress, Nrf2 is activated, translocates to nucleus, binds to antioxidant response element (ARE), thus upregulates a battery of antioxidant and detoxifying genes. This function of Nrf2 can be significant in the treatment of diseases, such as cancer, neurodegenerative, cardiovascular and pulmonary complications, where oxidative stress causes Nrf2 derangement. Nrf2 upregulating potential of phytochemicals has been explored, in facilitating cure for various ailments while, in cancer cells, Nrf2 upregulation causes chemoresistance. Therefore, Nrf2 emerges as a key regulator in oxidative stress-mediated diseases and Nrf2 silencing can open avenues in cancer treatment. This review summarizes Nrf2-ARE stress response mechanism and its role as a control point in oxidative stress-induced cellular dysfunctions including chronic inflammatory diseases.
Singh
Shruti
S
Herbal Research Section, Indian Institute of Toxicology Research, CSIR, PO Box-80, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India.
Vrishni
Sonal
S
Singh
Brijesh K
BK
Rahman
Irfan
I
Kakkar
Poonam
P
D000818:Animals; D002908:Chronic Disease; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
D051267:NF-E2-Related Factor 2; C115740:VPS52 protein, human; D033921:Vesicular Transport Proteins