Caffeine may reduce risk of Parkinson's disease

Coffee drinkers who worry that their morning fix might not be the healthiest habit may find comfort in a recent report. Scientists at Massachusetts General Hospital (MGH) have shown that caffeine is able to prevent the loss of the chemical signal that is depleted in Parkinson's disease. Published in the May 15th Journal of Neuroscience​, the study links caffeine's effects to the A2A receptor located on neural cells next to those that degenerate in Parkinson's patients. A2A receptors, which bind the molecule adenosine, are found in distinct areas of the brain, and their expression is restricted to the very cells that are targets of the dopaminergic neurons that go awry in Parkinson's disease. "The A2A receptor has a distinct advantage when it comes to treatment because it exists for the most part where you want to target your therapy. So there may be fewer side effects,"​ says Michael A. Schwarzschild, MD, PhD, Assistant Professor of Neurology at Massachussetts General Hospital​ and principal investigator. Caffeine acts as an antagonist to the A2A receptor, blocking its binding site and rendering it inactive. The scientists found that the effects of caffeine were mimicked by several known A2A antagonists as well as by genetic inactivation of the A2A receptor. The mouse study adds to epidemiological data published last year that documented how much coffee people drank and compared it to whether they developed Parkinson's. According to Schwarzschild, the results indicate that caffeine may be linked to a decreased risk of Parkinson's. "Once this association was found, people asked if caffeine had an effect on the disease, or rather, does Parkinson's have an effect on caffeine consumption,"​ says Jiang-Fan Chen, MD, PhD, assistant professor of Neurology at MGH and scientific co-director of the project. The current study shows that caffeine can prevent the biochemical hallmark of Parkinson's in the mouse model. "The animal results lend more weight to caffeine's neuroprotective nature,"​ says Schwarzschild. "But the results don't prove it, and they do not provide a rationale for changing caffeine consumption habits."​ Time will tell if the mouse data will translate to humans, he says. For their studies, Schwarzschild and his team used a mouse model. Mice exposed to a chemical called MPTP can develop Parkinson's-like symptoms because MPTP causes a decrease in brain dopamine. When the researchers pre-treated the mice with caffeine (at levels that would equal about a cup or two of coffee to humans), their brain dopamine levels remained near normal, and thus the MPTP toxicity was decreased. Interestingly, caffeine's neuroprotective effect may be closely linked to its stimulatory effect. Genetically altered mice that lack A2A receptors experienced none of the motor stimulation for which caffeine is so well known. "If caffeine is protective through the A2A receptor, more discrete targeting of this receptor may be a good therapy,"​ says Schwarzschild. A2A receptor antagonists are now entering human trials for the treatment of Parkinson's disease. "I look forward to seeing if this basic science lead will be relevant to clinical care,"​ says Schwarzschild.