Microglial Adenosine Receptors: From Preconditioning to Modulating the M1/M2 Balance in Activated Cells

Rafael Franco1,2, Alejandro Lillo3, Rafael Rivas-Santisteban1,2

  • 1CiberNed, Network Research Center, Neurodegenerative Diseases, Spanish National Health Institute Carlos III, 28034 Madrid, Spain.

Cells
|June 2, 2021
PubMed

Insights

Microglia, crucial for neuronal survival, have M1 (pro-inflammatory) and M2 (neuroprotective) states. Targeting adenosine receptors may shift microglia to the M2 phenotype, aiding neuroprotection and combating neurodegeneration.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Neuronal survival is dependent on glial cells, including astrocytes and microglia.
  • Microglial activation and neuronal death occur in both neurodegenerative diseases and normal aging.
  • Activated microglia exhibit M1 (pro-inflammatory) and M2 (neuroprotective) phenotypes, necessitating a balance for neuronal health.

Purpose of the Study:

  • To explore microglial activation mechanisms and their role in neuroprotection.
  • To investigate the potential of preconditioning microglia to enhance responses to damaging events.
  • To analyze adenosine receptors as therapeutic targets for modulating microglial phenotypes.

Main Methods:

  • Review of mechanisms underlying microglial activation.
  • Analysis of microglial responses to damaging events and preconditioning.
  • Discussion of adenosine receptors and their complexes with cannabinoids as therapeutic targets.

Main Results:

  • A balance between M1 and M2 microglial phenotypes is crucial for impeding chronic inflammation and ensuring neuronal survival.
  • Adenosine receptors play a role in microglial preconditioning and can be overexpressed in activated microglia.
  • Adenosine receptors and their complexes with cannabinoids show potential for microglia-mediated neuroprotection.

Conclusions:

  • Modulating microglial phenotypes, particularly shifting towards the M2 state, is vital for neuroprotection.
  • Adenosine receptors represent a promising therapeutic target for neurodegenerative conditions.
  • Targeting adenosine receptors and cannabinoid complexes could offer novel strategies for microglia-mediated neuroprotection.

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