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Following approval of antagonists in Parkinson’s disease therapy, the A 2A  adenosine receptor (A 2A R) is gaining interest as a target to combat a variety of diseases. This review focuses on the therapeutic potential of targeting A 2A R inside but also outside the central nervous system, more precisely to combat cardiac arrhythmias and to boost immune-based cancer therapies. The mechanism of regulation of the immune system by adenosine (Ado) is complex since several actors are involved, namely the enzymes that produce and degrade the compound and the four Ado receptors. Antagonists of A 2A  or andadenosine A 2B  Ado receptors lead to reduce their activation intracellular cAMP levels thus boosting immune responses. The literature search methodology consisted of reviewing the authors own collection of papers plus searches in the PubMed and Google Scholar databases from March 2021 to August 2022. There is a pending issue, namely, how to demonstrate the neuroprotective potential of A 2A R antagonists that would lead to delay neurodegenerative disease progression. In addition, A 2A R antagonists and, eventually, dual A 2A /A 2B  receptor antagonists have potential in the treatment of heart arrythmias and cancer. If adequate resources are allocated, it is a matter of time to confirm whether or not these possibilities become a reality.

The adenosine A 2A receptor is a therapeutic target in neurological, heart and oncogenic diseases