Do caffeine and more selective adenosine A receptor antagonists protect against dopaminergic neurodegeneration in Parkinson's disease?

The adenosine A 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 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 antagonists, as well as caffeine, as promising candidate therapeutics to fill the unmet need for disease modification of PD.