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Apoptosis signal-regulating kinase 1 as a therapeutic target

Yosuke Kawarazaki1, Hidenori Ichijo, Isao Naguro

  • 1The 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.

Expert Opinion on Therapeutic Targets
|March 26, 2014
PubMed
Abstract

Insights

Apoptosis signal-regulating kinase 1 (ASK1) is crucial for cellular stress responses but implicated in various diseases. While ASK1 has dual roles, new inhibitors show therapeutic promise, highlighting its potential as a drug target.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Organisms face constant stress, requiring robust stress response mechanisms for homeostasis.
  • Disrupted stress response systems are linked to numerous diseases.
  • Apoptosis signal-regulating kinase 1 (ASK1) is a key stress-responsive MAP3K involved in ROS, ER stress, and inflammatory responses.

Purpose of the Study:

  • To review the complex regulation of ASK1.
  • To elucidate ASK1's function in cellular stress responses.
  • To examine ASK1's involvement in diverse pathologies.

Main Methods:

  • Literature review of recent research on ASK1 regulation and function.
  • Analysis of ASK1's role in cellular stress pathways.
  • Examination of ASK1's contribution to disease pathogenesis.

Main Results:

  • ASK1 exhibits dual roles, offering protection in some diseases while exacerbating others.
  • ASK1 is implicated in cancer, neurodegenerative diseases, infections, diabetes, and cardiovascular diseases.
  • No current clinical therapies target ASK1 despite its disease relevance.

Conclusions:

  • ASK1 presents a complex role in disease, acting as both protective and detrimental.
  • Emerging ASK1 inhibitors (K811, MSC2032964A) demonstrate therapeutic potential in preclinical studies.
  • ASK1 is a significant emerging therapeutic target for various diseases.
Keywords:
apoptosisapoptosis signal-regulating kinase 1cancerendoplasmic reticulum stressinfectionneurodegenerative diseasesoxidative stress

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