How can caffeine alleviate the motor symptoms of Parkinson’s disease? – the implications of adenosine 2A receptor antagonism

Introduction and purpose: Parkinson’s disease (PD) is the second most common neurodegenerative disease, mainly characterized by motor impairment with symptoms including rigidity, bradykinesia, rest tremor and imbalance. It develops upon degeneration of dopaminergic neurons in the substantia nigra associated with neuroinflammatory process initiated by alpha-synuclein deposits. Although, levodopa replacement therapy is the gold-standard treatment, majority of the treated patients develop dyskinesia as the side effect, resulting from altered function of dopamine receptors. It is thought that the abnormal pulsate release of dopamine can be prevented by antagonism of adenosine 2A receptors (A2ARs). Aim of the study: This review aims to outline the action mechanism of A2AR antagonism on motor performance, and thus evaluate the suggested implications of coffee consumption in PD. Material and method: The involvement of A2ARs in the pathology and treatment of PD has been analyzed based on the findings of many published studies examining the effects of A2AR modulation. Results: Blockage of A2ARs enhances the action of dopamine via D2 receptors on striatopallidal neurons, decreasing their hyperactivity, and exerts neuroprotective effect, suppressing the neuroinflammation. Conclusions: Istradefylline, being the only approved A2AR antagonist, was able to reduce total cumulative dose of levodopa, improve motor control, alleviate postural abnormalities, and provide a reduction in daily ‘off’ time experienced by patients. Recent findings suggest the effects of drinking one cup of coffee are comparable with ones obtained by the newly introduced medication, presumably via shared action mechanism by A2AR inhibition.