For their studies, Schwarzschild and his team used a mouse model that mimics the features of Parkinson's diseasenamely, neural degeneration in the brain associated with a depletion of the neurotransmitter dopamine. Mice exposed to a chemical called MPTP can develop Parkinson's-like symptoms because MPTP causes a decrease in brain dopamine. When the researchers pretreated 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 experience none of the motor stimulation for which caffeine is so well known.
Dopamine replacement is the standard treatment for Parkinson's disease today. Despite this treatment, the disease continues to progress, often accompanied by motor side effects of the therapy. A2A receptor antagonists can enhance motor function and perhaps even slow disease progression without these complications. "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.
A complementary paper by Harvard researchers that looks at extensive epidemiological data on caf
Contact: Georgia W. Peirce
Massachusetts General Hospital