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lüll An important role of Nrf2-ARE pathway in the cellular defense mechanism Lee JM; Johnson JAJ Biochem Mol Biol 2004[Mar]; 37 (2): 139-43The antioxidant responsive element (ARE) is a cis-acting regulatory element of genes encoding phase II detoxification enzymes and antioxidant proteins, such as NAD(P)H: quinone oxidoreductase 1, glutathione S-transferases, and glutamate-cysteine ligase. Interestingly, it has been reported that Nrf2 (NF-E2-related factor 2) regulates a wide array of ARE-driven genes in various cell types. Nrf2 is a basic leucine zipper transcription factor, which was originally identified as a binding protein of locus control region of beta-globin gene. The DNA binding sequence of Nrf2 and ARE sequence are very similar, and many studies demonstrated that Nrf2 binds to the ARE sites leading to up-regulation of downstream genes. The function of Nrf2 and its downstream target genes suggests that the Nrf2-ARE pathway is important in the cellular antioxidant defense system. In support of this, many studies showed a critical role of Nrf2 in cellular protection and anti-carcinogenicity, implying that the Nrf2-ARE pathway may serve as a therapeutic target for neurodegenerative diseases and cancers, in which oxidative stress is closely implicated.|*Immunity, Cellular[MESH]|Animals[MESH]|Cytoprotection[MESH]|DNA-Binding Proteins/genetics/*immunology/*physiology[MESH]|Gene Expression Regulation, Enzymologic[MESH]|Humans[MESH]|Leucine Zippers/genetics[MESH]|Models, Biological[MESH]|NF-E2-Related Factor 2[MESH]|Response Elements[MESH]|Trans-Activators/genetics/*immunology/*physiology[MESH] |