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关于ASK1信号传导的最新见解:疾病中的机制、调控及治疗潜力

Updated insights on ASK1 signaling: mechanisms, regulation, and therapeutic potential in diseases.

作者信息

Thakur Divyanshi, Nandi Aniket, Gaur Yash Kumar, Chandrabose Karthikeyan, Waiker Digambar Kumar, Gupta Ghanshyam Das, Sharma Kalicharan

机构信息

Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab, 142001, India.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

出版信息

Mol Cell Biochem. 2025 Jun 14. doi: 10.1007/s11010-025-05330-y.

Abstract

Apoptosis signal-regulating kinase 1 (ASK1) is a serine-threonine kinase, that is a member of the mitogen-activated protein kinase kinase (MAP3K) family, which is expressed or incorporated in nucleated cells which leads to the activation of multiple mitogen-activated protein kinases (MAPK) to regulate cell stress, tumour necrosis factor-α (TNF-α) ligand, lipopolysaccharides and apoptosis. ASK1 gets activated by the ROS, oxidative stress, endoplasmic stress (ER) and various inflammatory cytokines. Dysregulation of ASK1 can lead to various diseases like neurodegenerative disease, cardiovascular disease, cancer, and various other metabolic diseases such as diabetes. This review summarizes ASK1's structure, its family, regulation, and its dual role in disease, highlighting its therapeutic potential for oxidative stress and inflammation-driven conditions while emphasizing the need for further clinical research. Inhibition of ASK1 demonstrates promising potential in treating fibrosis and various other diseases. We also discuss the dual role of ASK1 in both cancer initiation and suppression. Additionally, we explore ASK1 as a therapeutic target in diseases driven by oxidative stress and inflammation, emphasizing the need for further research to support its clinical translation.

摘要

凋亡信号调节激酶1(ASK1)是一种丝氨酸 - 苏氨酸激酶,属于丝裂原活化蛋白激酶激酶(MAP3K)家族成员,在有核细胞中表达或整合,可导致多种丝裂原活化蛋白激酶(MAPK)激活,从而调节细胞应激、肿瘤坏死因子-α(TNF-α)配体、脂多糖和细胞凋亡。ASK1可被活性氧(ROS)、氧化应激、内质网应激(ER)和各种炎性细胞因子激活。ASK1失调可导致多种疾病,如神经退行性疾病、心血管疾病、癌症以及糖尿病等各种其他代谢性疾病。本综述总结了ASK1的结构、家族、调节及其在疾病中的双重作用,突出了其在氧化应激和炎症驱动疾病中的治疗潜力,同时强调了进一步临床研究的必要性。抑制ASK1在治疗纤维化和其他各种疾病方面显示出有前景的潜力。我们还讨论了ASK1在癌症发生和抑制中的双重作用。此外,我们探讨了ASK1作为氧化应激和炎症驱动疾病治疗靶点的可能性,强调需要进一步研究以支持其临床转化。

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