Adenosine A2A receptors and brain injury: broad spectrum of neuroprotection, multifaceted actions and "fine tuning" modulation

Prog Neurobiol. 2007 Dec;83(5):310-31. doi: 10.1016/j.pneurobio.2007.09.002. Epub 2007 Sep 29.


This review summarizes recent developments that have contributed to understand how adenosine receptors, particularly A2A receptors, modulate brain injury in various animal models of neurological disorders, including Parkinson's disease (PD), stroke, Huntington's disease (HD), multiple sclerosis, Alzheimer's disease (AD) and HIV-associated dementia. It is clear that extracellular adenosine acting at adenosine receptors influences the functional outcome in a broad spectrum of brain injuries, indicating that A2A Rs may modulate some general cellular processes to affect neuronal cells death. Pharmacological, neurochemical and molecular/genetic approaches to the complex actions of A2A receptors in different cellular elements suggest that A2A receptor activation can be detrimental or protective after brain insults, depending on the nature of brain injury and associated pathological conditions. An interesting concept that emerges from these studies is A2A R's ability to fine tune neuronal and glial functions to produce neuroprotective effects. While the data presented here clearly highlight the complexity of using adenosinergic agents therapeutically in PD and other neurodegenerative disorders and point out many areas for further inquiry, they also confirm that adenosine receptor ligands, particularly A2A receptor ligands, have many promising characteristics that encourage the pursuit of their therapeutic potential.

Publication types

  • Review

MeSH terms

  • Adenosine / metabolism*
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Brain / physiopathology
  • Brain Diseases / drug therapy
  • Brain Diseases / genetics
  • Brain Diseases / metabolism*
  • Brain Injury, Chronic / genetics
  • Brain Injury, Chronic / metabolism
  • Brain Injury, Chronic / physiopathology
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cytoprotection / drug effects
  • Cytoprotection / physiology*
  • Humans
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / physiopathology
  • Neuroprotective Agents / pharmacology
  • Receptor, Adenosine A2A / metabolism*


  • Neuroprotective Agents
  • Receptor, Adenosine A2A
  • Adenosine