Purinergic P2X7 receptor as a potential therapeutic target in depression

Biochem Pharmacol. 2024 Jan:219:115959. doi: 10.1016/j.bcp.2023.115959. Epub 2023 Dec 3.

Abstract

The elaborate mechanisms of depression have always been a research hotspot in recent years, and the pace of research has never ceased. The P2X7 receptor (P2X7R) belongs to one of the adenosine triphosphates (ATP)-gated cation channels that exist widely in brain tissues and play a prominent role in the regulation of depression-related pathology. To date, the role of purinergic P2X7R in the mechanisms underlying depression is not fully understood. In this review, we conclude that the purinergic receptor P2X7 is a potential therapeutic target for depression based on research results published over the past 5 years in Google Scholar and the National Library of Medicine (PubMed). Additionally, we introduced the functional characteristics of P2X7R and confirmed that excessive activation of P2X7R led to increased release of inflammatory cytokines, which eventually contributed to depression. Furthermore, the inhibition of P2X7R produced antidepressant-like effects in animal models of depression, further proving that P2X7R signalling mediates depression-like behaviours. Finally, we summarised related studies on drugs that exert antidepressant effects by regulating the expression of P2X7R. We hope that the conclusions of this review will provide information on the role of P2X7R in the neuropathophysiology of depression and novel therapeutic targets for the treatment of depression.

Keywords: Antidepressant; Depression; Expression levels; P2X7R; Targets.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Cytokines / metabolism
  • Depression* / drug therapy
  • Purinergic P2X Receptor Antagonists / pharmacology
  • Purinergic P2X Receptor Antagonists / therapeutic use
  • Receptors, Purinergic P2X7* / metabolism
  • Signal Transduction

Substances

  • Receptors, Purinergic P2X7
  • Cytokines
  • Antidepressive Agents
  • Adenosine Triphosphate
  • Purinergic P2X Receptor Antagonists