Abstract
Adenosine A2A receptors (A2A Rs) are highly expressed in the human striatum, and at lower densities in the cerebral cortex, the hippocampus, and cells of the immune system. Antagonists of these receptors are potentially useful for the treatment of motor fluctuations, epilepsy, postischemic brain damage, or cognitive impairment, and for the control of an immune checkpoint during immunotherapy of cancer. A2A R agonists may suppress transplant rejection and graft-versus-host disease; be used to treat inflammatory disorders such as asthma, inflammatory bowel disease, and rheumatoid arthritis; be locally applied to promote wound healing and be employed in a strategy for transient opening of the blood-brain barrier (BBB) so that therapeutic drugs and monoclonal antibodies can enter the brain. Increasing A2A R signaling in adipose tissue is also a potential strategy to combat obesity. Several radioligands for positron emission tomography (PET) imaging of A2A Rs have been developed in recent years. This review article presents a critical overview of the potential therapeutic applications of A2A R ligands, the use of A2A R imaging in drug development, and opportunities and limitations of PET imaging in future research.
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