How does adenosine control neuronal dysfunction and neurodegeneration?

Abstract in brief

• Adenosine in the brain primarily regulates neuronal activity by activating inhibitory A1 receptors (A1R) and facilitatory A2 receptors (A2R), helping to control excitatory signals and support synaptic plasticity.
• During brain injury or stress, large amounts of adenosine are released, which can initially protect neurons by limiting damage, but prolonged activation of A2Rs may increase brain damage, meaning that balancing A1R and A2R activity is crucial for neuroprotection.
• The functions and signaling pathways of adenosine receptors are complex and diverse, involving various G proteins and noncanonical pathways, making it important to carefully modulate these receptors to maximize neuroprotection and prevent damage in conditions like epilepsy, depression, Alzheimer’s, or Parkinson’s disease.]