Proceedings of the Japan Academy, Series B
Online ISSN : 1349-2896
Print ISSN : 0386-2208
Reviews
Therapeutic targets in the ASK1-dependent stress signaling pathways
Ryoichi HAYAKAWATeruyuki HAYAKAWAKohsuke TAKEDAHidenori ICHIJO
Author information
JOURNALS FREE ACCESS

2012 Volume 88 Issue 8 Pages 434-453

Details
Abstract

Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family that activates downstream MAP kinases (MAPKs), c-Jun N-terminal kinases (JNKs) and p38 MAPKs, in response to various stresses, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, lipopolysaccharide, and calcium overload. Activation of the JNK and p38 pathways induces stress responses such as cell death, differentiation, and the production of inflammatory cytokines. A series of studies using ASK1-deficient mice have indicated that ASK1 plays important roles in many stress-related diseases, including cardiovascular and neurodegenerative diseases, suggesting that small compounds that inhibit ASK1 activity could possibly be used for the amelioration of the development and/or progression of these diseases. In this review, we provide an overview of the pathophysiological roles of ASK1-dependent signaling pathways and discuss the mechanistic basis for how these could serve as potential therapeutic targets.

(Communicated by Takao SEKIYA, M.J.A.)

Information related to the author
© 2012 The Japan Academy
Previous article Next article
feedback
Top