Protective Effects of Caffeine in Animal Models of Parkinson's Disease

Michael A. Schwarzchild, MD, Ph.D.
Massachusetts General Hospital
R01ES10804

Background: During the past decade several laboratory and epidemiologic studies have suggested that caffeine use reduces the risk of Parkinson's disease by preventing the loss of dopamine producing neurons located in the substania nigra region of the brain. These authors review the evidence that caffeine and other more specific antagonists of the adenosine A2A receptor protect dopamine producing neurons in several animal toxicity models for Parkinson's disease.

Advance: The demonstration that caffeine and more specific A2A antagonists protect dopaminergic neurons in animal models of Parkinson's disease has pathophysiologic, epidemiologic, and therapeutic significance. Understanding the neurobiology of the A2A and other adenosine receptors provides insight into the role of endogenous adenosine in basal ganglia biology and Parkinson's pathophysiology.

Implication: Although the cellular and molecular mechanisms by which A2A receptors contribute to neuronal cell death have not been revealed, several possibilities have emerged. Preliminary clinical data have substantiated the antiparkinsonian benefits of caffeine and other A2A receptor blockers. Potential neuroprotective benefits from the use of A2A receptor antagonists suggest the possibility of improved treatments and outcomes for Parkinson's disease.

Citation: Schwarzschild MA, Xu K, Oztas E, Petzer JP, Castagnoli K, Castagnoli N Jr, Chen JF. Neuroprotection by caffeine and more specific A2A receptor antagonists in animal models of Parkinson's disease. Neurology. 2003 Dec 9;61(11 Suppl 6):S55-61.