Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Trends Pharmacol Sci. 2013 Jun;34(6):340-6. doi: 10.1016/j.tips.2013.04.005. Epub 2013 May 9.
The Keap1-Nrf2 pathway plays a crucial role in determining the sensitivity of cells to chemical and/or oxidative insults by regulating the basal and inducible expression of detoxification and antioxidant enzymes, ABC transporters, and other stress response enzymes and/or proteins. Increasing attention has been focused on the roles that the Keap1-Nrf2 pathway plays in the protection of our body against drug toxicity and stress-induced diseases. Simultaneously, Nrf2 has been recognized to promote oncogenesis and resistance to chemotherapeutic drugs. Cancer cells hijack Nrf2 activity to support their malignant growth and thus Nrf2 has emerged as a therapeutic target. Translational studies of the Keap1-Nrf2 system, from mechanistic understanding to clinical applications, are now important to improve human health.
KEAP1-NRF2 通路通过调节解毒和抗氧化酶、ABC 转运蛋白和其他应激反应酶和/或蛋白的基础和诱导表达,在决定细胞对化学和/或氧化应激的敏感性方面发挥着关键作用。人们越来越关注 KEAP1-NRF2 通路在保护我们的身体免受药物毒性和应激诱导性疾病方面的作用。同时,Nrf2 已被认为可促进肿瘤发生和对化疗药物的耐药性。癌细胞劫持 Nrf2 活性以支持其恶性生长,因此 Nrf2 已成为治疗靶点。KEAP1-NRF2 系统的转化研究,从机制理解到临床应用,对于改善人类健康非常重要。