Glycogen Synthase Kinase 3 (GSK3): Its Role and Inhibitors

Curr Top Med Chem. 2020;20(17):1522-1534. doi: 10.2174/1568026620666200516153136.

Abstract

Glycogen Synthase Kinase 3 (GSK3) is one of the Serine/Threonine protein kinases, which has gained a lot of attention for its role in a variety of pathways. It has two isoforms, GSK3α and GSK3β. However, GSK3β is highly expressed in different areas of the brain and has been implicated in Alzheimer's disease as it is involved in tau phosphorylation. Due to its high specificity concerning substrate recognition, GSK3 has been considered as an important target. In the last decade, several GSK3 inhibitors have been reported and two molecules are in clinical trials. This review collates the information published in the last decade about the role of GSK3 in Alzheimer's disease and progress in the development of its inhibitors. Using this collated information, medicinal chemists can strategize and design novel GSK3 inhibitors that could be useful in the treatment of Alzheimer's disease.

Keywords: Alzheimer`s disease; Cancer; Glycogen Synthase Kinase 3; Inflammation; Inhibitors; Tideglusib.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 / metabolism
  • Humans
  • Molecular Structure
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*

Substances

  • Protein Kinase Inhibitors
  • Glycogen Synthase Kinase 3