期刊
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
卷 2021, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2021/6635460
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资金
- National Natural Science Foundation of China [31960191]
- Science and Technology Innovation Leading Academics of National High-level Personnel of Special Support Program [GKFZ-2018-29]
- Guizhou Provincial ST Foundation [QKHJC-ZK-2021-ZD026]
- S&T Foundation of Zunyi Science and Technology Bureau [ZSKH-HZ-Z-2020212, ZSKH-HZ-Z-2020222, ZSKH-HZ-Z-2020249, ZSK-RC-2020-1]
Oxidative stress plays a significant role in senescence-related diseases and aging, with the Keap1-Nrf2 system serving as a key player in monitoring oxidative stress and controlling the transcription of antioxidant enzymes. The complex regulatory network around Keap1-Nrf2 signaling involves multiple pathways, highlighting the intricate mechanisms involved in oxidative stress and aging research.
Oxidative stress, a term that describes the imbalance between oxidants and antioxidants, leads to the disruption of redox signals and causes molecular damage. Increased oxidative stress from diverse sources has been implicated in most senescence-related diseases and in aging itself. The Kelch-like ECH-associated protein 1- (Keap1-) nuclear factor-erythroid 2-related factor 2 (Nrf2) system can be used to monitor oxidative stress; Keap1-Nrf2 is closely associated with aging and controls the transcription of multiple antioxidant enzymes. Simultaneously, Keap1-Nrf2 signaling is also modulated by a more complex regulatory network, including phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), protein kinase C, and mitogen-activated protein kinase. This review presents more information on aging-related molecular mechanisms involving Keap1-Nrf2. Furthermore, we highlight several major signals involved in Nrf2 unbinding from Keap1, including cysteine modification of Keap1 and phosphorylation of Nrf2, PI3K/Akt/glycogen synthase kinase 3 beta, sequestosome 1, Bach1, and c-Myc. Additionally, we discuss the direct interaction between Keap1-Nrf2 and the mammalian target of rapamycin pathway. In summary, we focus on recent progress in research on the Keap1-Nrf2 system involving oxidative stress and aging, providing an empirical basis for the development of antiaging drugs.
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