Apoptosis signal-regulating kinase 1 as a therapeutic target.

INTRODUCTION: All organisms are ordinarily exposed to various stresses. It is important for organisms to possess appropriate stress response mechanisms and to maintain homeostasis because the disruption of a stress response system can cause various diseases. Apoptosis signal-regulating kinase 1 (ASK1) is one of the stress-responsive MAP3Ks. ASK1 plays an important role in the response to reactive oxygen species (ROS), endoplasmic reticulum stress and pro-inflammatory cytokines, and it is involved in the pathogenesis of various diseases. AREAS COVERED: In this review, the authors describe recent literature concerning the intricate and elaborate regulation system of ASK1, the function of ASK1 during a cellular stress response and the involvement of ASK1 in many diseases, including cancer, neurodegenerative diseases, infections, diabetes and cardiovascular diseases. EXPERT OPINION: In certain disease conditions, ASK1 plays a protective role, whereas ASK1 can exacerbate the pathology of other diseases. Although ASK1 is involved in various diseases, there is no therapy or drug that targets ASK1 for use in a clinical setting. Recently, ASK1 inhibitors (K811 and MSC2032964A) have emerged, and their therapeutic potentials have been tested in vivo. ASK1 is currently receiving considerable attention as a new therapeutic target.