Neurology 2002;58:1154-1160
© 2002 American Academy of Neurology
Views & Reviews
Caffeinated clues and the promise of adenosine A2A antagonists in PD
Michael A. Schwarzschild, MD PhD,
Jiang-Fan Chen, MD PhD and
Alberto Ascherio, MD DrPH
From the Department of Neurology (Dr. Schwarzschild), Massachusetts General Hospital; Department of Neurology (Dr. Chen), Boston University School of Medicine; and Department of Nutrition (Dr. Ascherio), Harvard School of Public Health, Boston, MA.
Address correspondence and reprint requests to Dr. Michael A. Schwarzschild, Center for Aging, Genetics and Neurodegeneration, MGH, 114 16th St., Charlestown, MA 02129; e-mail: michaels{at}helix.mgh.harvard.edu
Large prospective epidemiologic studies have linked the consumption of coffee and other caffeinated beverages to a reduced risk of subsequently developing PD. Caffeine as well as more specific antagonists of the adenosine A2A receptor have also now been found to attenuate neurotoxicity in a mouse model of PD. The convergence of these epidemiologic and laboratory data supports the possibility that caffeine may reduce the risk of developing PD. However, a neuroprotective effect of caffeine in PD remains unproven; current evidence does not provide a rational basis for recommending caffeine consumption to modify the risk or progression of PD. In addition to possessing neuroprotective potential, caffeine and other A2A antagonists have long been known to acutely reverse motor deficits in a variety of PD models. This symptomatic antiparkinsonian benefit of blocking A2A receptors, coupled with their remarkably restricted expression in the basal ganglia, have made A2A antagonists attractive targets for drug development. Now, with the prospect of a neuroprotective bonus, the novel therapeutic potential of A2A antagonists appears all the more promising just as they are entering clinical trials for PD.
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