ASK1 and its role in cardiovascular and other disorders: available treatments and future prospects

Expert Rev Proteomics. 2019 Oct;16(10):857-870. doi: 10.1080/14789450.2019.1676735. Epub 2019 Oct 17.

Abstract

Introduction: Apoptosis signal-regulating kinase 1 (ASK1), also known as MAP3K5, is a member of mitogen-activated protein kinase kinase kinase (MAP3K) family and is well reported as crucial in the regulation of the JNK and P38 pathways. ASK1 is activated in response to a diverse array of stresses such as endoplasmic reticulum stress, lipopolysaccharides, tumor necrosis factor alpha, and reactive oxygen species. The activation of ASK1 induces various stress responses. Areas covered: Considering ASK1 as an important therapeutic drug target, here we have discussed the role of ASK1 in the progression of various diseases. We have also provided an overview of the available inhibitors for ASK1. The success of computational-based approaches toward ASK1 inhibitor design has also been discussed. Expert opinion: A number of reports have outlined the prominent role of ASK1 in the pathogenesis of several diseases. The discovery of novel ASK1 inhibitors would have a wide range of applications in medical science. In-silico techniques have been successfully used in the design of some novel ASK1 inhibitors. The use of machine learning-based approaches in combination with structure-based virtual screening (SBVS) and ligand-based virtual screening (LBVS) will be helpful toward the development of potent ASK1 inhibitors.

Keywords: ASK1; MAPK pathway; diseases; signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis / genetics*
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / pathology
  • Endoplasmic Reticulum Stress / genetics
  • Gene Expression Regulation / genetics
  • Humans
  • MAP Kinase Kinase Kinase 5 / antagonists & inhibitors
  • MAP Kinase Kinase Kinase 5 / genetics*
  • MAP Kinase Signaling System / genetics
  • Machine Learning
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • p38 Mitogen-Activated Protein Kinases / genetics

Substances

  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 5
  • MAP3K5 protein, human