Tryptophanyl-tRNA Synthetase as a Potential Therapeutic Target

Int J Mol Sci. 2021 Apr 26;22(9):4523. doi: 10.3390/ijms22094523.

Abstract

Tryptophanyl-tRNA synthetase (WRS) is an essential enzyme that catalyzes the ligation of tryptophan (Trp) to its cognate tRNAtrp during translation via aminoacylation. Interestingly, WRS also plays physiopathological roles in diseases including sepsis, cancer, and autoimmune and brain diseases and has potential as a pharmacological target and therapeutic. However, WRS is still generally regarded simply as an enzyme that produces Trp in polypeptides; therefore, studies of the pharmacological effects, therapeutic targets, and mechanisms of action of WRS are still at an emerging stage. This review summarizes the involvement of WRS in human diseases. We hope that this will encourage further investigation into WRS as a potential target for drug development in various pathological states including infection, tumorigenesis, and autoimmune and brain diseases.

Keywords: Alzheimer’s disease; IFN-γ; cancer; kynurenine pathway; sepsis; tryptophan metabolism; tryptophanyl-tRNA synthetase.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease
  • Humans
  • Interferon-gamma / pharmacology
  • Neoplasms
  • Sepsis
  • Tryptophan / metabolism
  • Tryptophan-tRNA Ligase / genetics
  • Tryptophan-tRNA Ligase / immunology
  • Tryptophan-tRNA Ligase / metabolism*
  • Tryptophan-tRNA Ligase / physiology*

Substances

  • Interferon-gamma
  • Tryptophan
  • Tryptophan-tRNA Ligase