Do caffeine and more selective adenosine A(2A) receptor antagonists protect against dopaminergic neurodegeneration in Parkinson’s disease?

The adenosine A(2A) receptor is a major target of caffeine, the most widely used psychoactive substance worldwide. Large epidemiological studies have long shown caffeine consumption is a strong inverse predictor of Parkinson’s disease (PD). In this review, we first examine the epidemiology of caffeine use vis-à-vis PD and follow this by looking at the evidence for adenosine A(2A) receptor antagonists as potential neuroprotective agents. There is a wealth of accumulating biological, epidemiological and clinical evidence to support the further investigation of selective adenosine A(2A) antagonists, as well as caffeine, as promising candidate therapeutics to fill the unmet need for disease modification of PD.