title: Apoptosis signal-regulating kinase 1 as a therapeutic target.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The University of Tokyo, Graduate School of Pharmaceutical Sciences, Cell Signaling , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 , Japan +81 3 5841 4858 ; +81 3 5841 4798 ; ichijo@mol.f.u-tokyo.ac.jp.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kawarazaki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ichijo
authors.forename: Isao
authors.initials: I
authors.lastname: Naguro
mesh_terms: D000818:Animals; D017209:Apoptosis; D003110:Colonic Neoplasms / Q000209:etiology; D003920:Diabetes Mellitus / Q000209:etiology; D006801:Humans; D048848:MAP Kinase Kinase Kinase 5 / Q000037:antagonists & inhibitors* / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000209:etiology; D010766:Phosphorylation; D012878:Skin Neoplasms / Q000209:etiology; D013274:Stomach Neoplasms / Q000209:etiology; D054875:Ubiquitination
chemical_list: D048848:MAP Kinase Kinase Kinase 5
keywords: apoptosis; apoptosis signal-regulating kinase 1; cancer; endoplasmic reticulum stress; infection; neurodegenerative diseases; oxidative stress