Targeting the AMPK/Nrf2 Pathway: A Novel Therapeutic Approach for Acute Lung Injury

安普克 急性呼吸窘迫综合征 氧化应激 KEAP1型 蛋白激酶A 信号转导 医学 转录因子 炎症 癌症研究 细胞生物学 激酶 免疫学 生物信息学 生物 内科学 生物化学 基因
作者
Qianxia Huang,Yingcong Ren,Ping Yuan,Ma Huang,Guoyue Liu,Yuanzhi Shi,Guiyang Jia,Miao Chen
出处
期刊:Journal of Inflammation Research [Dove Medical Press]
卷期号:Volume 17: 4683-4700 被引量:9
标识
DOI:10.2147/jir.s467882
摘要

ALI(acute lung injury) is a severe respiratory dysfunction caused by various intrapulmonary and extrapulmonary factors. It is primarily characterized by oxidative stress and affects the integrity of the pulmonary barrier. In severe cases, ALI can progress to ARDS(acute respiratory distress syndrome), a condition that poses a serious threat to the lives of affected patients. To date, the etiological mechanisms underlying ALI remain elusive, and available therapeutic options are quite limited. AMPK(AMP-activated protein kinase), an essential serine/threonine protein kinase, performs a pivotal function in the regulation of cellular energy levels and cellular regulatory mechanisms, including the detection of redox signals and mitigating oxidative stress. Meanwhile, Nrf2(nuclear factor erythroid 2-related factor 2), a critical transcription factor, alleviates inflammation and oxidative responses by interacting with multiple signaling pathways and contributing to the modulation of oxidative enzymes associated with inflammation and programmed cell death. Indeed, AMPK induces the dissociation of Nrf2 from Keap1(kelch-like ECH-associated protein-1) and facilitates its translocation into the nucleus to trigger the transcription of downstream antioxidant genes, ultimately suppressing the expression of inflammatory cells in the lungs. Given their roles, AMPK and Nrf2 hold promise as novel treatment targets for ALI. This study aimed to summarise the current status of research on the AMPK/Nrf2 signaling pathway in ALI, encompassing recently reported natural compounds and drugs that can activate the AMPK/Nrf2 signaling pathway to alleviate lung injury, and provide a theoretical reference for early intervention in lung injury and future research on lung protection.
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