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Adenosine A₂A receptor as a dual-acting molecular switch: Glial morphological changes and neurovascular tissue remodeling in neuroinflammation and neurodegeneration - PubMed

7 days ago
  • #Neurodegeneration
  • #Neuroinflammation
  • #Adenosine A₂A receptor
  • Adenosine A₂A receptor (A₂AR) plays a dual role in neuroinflammation and neurodegeneration.
  • Moderate A₂AR activation reduces acute inflammation and supports neuronal survival, while prolonged activation increases glial activation and cytokine production.
  • A₂AR signaling in microglia and astrocytes affects NF-κB and MAPK pathways, influencing oxidative stress, BBB stability, and excitotoxicity.
  • Short-term A₂AR activation boosts anti-inflammatory cytokines like IL-10 and enhances neurotrophic support via BDNF.
  • A₂AR antagonists (e.g., istradefylline, SCH58261) show potential in reducing microglial activation and providing neuroprotection.
  • Complete A₂AR blockage disrupts adaptive immune control, highlighting the need for cell-specific modulation.
  • Therapeutic strategies aim to target A₂AR in specific cell populations (astrocytes, microglia) while preserving peripheral immunoregulation.
  • Understanding temporal and cell-specific A₂AR dynamics is key for developing neuroprotective treatments.