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

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.