Molecular and Structural Insight into Adenosine A 2A Receptor in Neurodegenerative Disorders: A Significant Target for Efficient Treatment Approach

All biological tissues and bodily fluids include the autacoid adenosine. The P1 class of purinergic receptors includes adenosine receptors. Four distinct G-protein-coupled receptors on the cellular membrane mediate the effects of adenosine, whose cytoplasmic content is regulated by producing/degrading enzymes and nucleoside transporters. A 2A receptor has received a great deal of attention in recent years because it has a wide range of potential therapeutic uses. A 2B and, more significantly, A 2A receptors regulate numerous physiological mechanisms in the central nervous system (CNS). The inferior targetability of A 2B receptors towards adenosine points that they might portray a promising medicinal target since they are triggered only under pharmacological circumstances (when adenosine levels rise up to micromolar concentrations). The accessibility of specific ligands for A 2B receptors would permit the exploration of such a theory. A 2A receptors mediate both potentially neurotoxic and neuroprotective actions. Hence, it is debatable to what extent they play a role in neurodegenerative illnesses. However, A 2A receptor blockers have demonstrated clear antiparkinsonian consequences, and a significant attraction exists in the role of A 2A receptors in other neurodegenerative disorders. Amyloid peptide extracellular accumulation and tau hyperphosphorylation are the pathogenic components of AD that lead to neuronal cell death, cognitive impairment, and memory loss. Interestingly, in vitro and in vivo research has shown that A 2A adenosine receptor antagonists may block each of these clinical symptoms, offering a crucial new approach to combat a condition for which, regrettably, only symptomatic medications are currently available. At least two requirements must be met to determine whether such receptors are a target for diseases of the CNS: a complete understanding of the mechanisms governing A 2A -dependent processes and the availability of ligands that can distinguish between the various receptor populations. This review concisely summarises the biological effects mediated by A 2A adenosine receptors in neurodegenerative disorders and discusses the chemical characteristics of A 2A adenosine receptor antagonists undergoing clinical trials. Graphical Abstract Selective A 2A receptor blocker against neurodegenerative disorders