Modulation of Microglial Function by ATP-Gated P2X7 Receptors: Studies in Rat, Mice and Human

Manju Tewari1, Stephanie Michalski1, Terrance M Egan1

  • 1Department of Pharmacology and Physiology, and The Henry and Amelia Nasrallah Institute for Translational Neuroscience, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.

Cells
|January 22, 2024
PubMed

Insights

P2X receptors, particularly P2X7, are key in innate immunity. Microglia, the brain

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • P2X receptors are ATP-gated ion channels involved in cellular responses.
  • P2X7 receptors require high ATP concentrations and act as damage-associated molecular patterns.
  • Microglia are the primary immune cells in the central nervous system.

Purpose of the Study:

  • To review the role of extracellular ATP and P2X receptors in central nervous system innate immunity.
  • To focus on microglia activation by ATP and its analogs.
  • To highlight human studies of P2X7R where possible.

Main Methods:

  • Literature review of original works and relevant reviews.
  • Focus on studies involving microglia activation by ATP and BzATP.
  • Emphasis on P2X7 receptor function in innate immunity.

Main Results:

  • Extracellular ATP and P2X receptors initiate and modulate innate immune responses in the CNS.
  • Microglia activation by ATP is central to neuroinflammation.
  • P2X7 receptor's role in immune signaling is significant, especially in response to tissue damage.

Conclusions:

  • P2X receptors, particularly P2X7, are critical mediators of innate immunity in the CNS.
  • Microglia play a pivotal role in ATP-mediated neuroinflammation.
  • Understanding P2X7R function is crucial for developing therapies for neurological disorders.

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