Zinc-dependent deacetylases (HDACs) as potential targets for treating Alzheimer's disease

Bioorg Med Chem Lett. 2022 Nov 15:76:129015. doi: 10.1016/j.bmcl.2022.129015. Epub 2022 Oct 5.

Abstract

Alzheimer's disease (AD) as the most prevalent dementia type has become one of the greatest threats to the health and life of the elder people worldwide. Although there has been a great effort in the discovery of anti-AD drugs, those approval drugs only demonstrated the temporarily relieving the symptoms without completely stopping the progression of the neuropathology. It is very urgent and reasonable to develop more effective agents against other therapeutic targets. In the last two decades, zinc-dependent deacetylases (HDACs) have attracted much attention as an important group of epigenetic targets in drug discovery, because five HDAC inhibitors have been approved for clinically treating cancers. This review is to summarize the possible roles of HDACs in AD pathophysiology and their inhibitors used in AD studies. And the future perspectives related to HDACs as epigenetic targets for treating AD by their selective inhibitors, multi-target inhibitors or PROTACs are also discussed.

Keywords: Alzheimer’s disease; HDAC; HDAC6; Inhibitor; PROTAC.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease* / drug therapy
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use
  • Histone Deacetylases
  • Humans
  • Neoplasms* / drug therapy
  • Zinc

Substances

  • Histone Deacetylase Inhibitors
  • Zinc
  • Histone Deacetylases