The adenosine A2A receptor is a therapeutic target in neurological, heart and oncogenic diseases

Abstract

Introduction: Following approval of antagonists in Parkinson's disease therapy, the A_2A adenosine receptor (A_2AR) is gaining interest as a target to combat a variety of diseases.

Areas covered: This review focuses on the therapeutic potential of targeting A_2AR 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.

Expert opinion: There is a pending issue, namely, how to demonstrate the neuroprotective potential of A_2AR antagonists that would lead to delay neurodegenerative disease progression. In addition, A_2AR 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.

Keywords: Adenosine deaminase; Anti-cancer immunotherapy; Cancer; adenosine receptors; arrythmias; atrial fibrillation; etrumadenant; istradefylline; neurodegenerative diseases; neuroprotection.