ABSTRACT
Introduction 147
The Epidemiology of Caffeine and Parkinson’s Disease 148
Study Design 148
Case-Control Studies 149
Cohort Studies 149
Neuroprotection by Caffeine and More Specific Adenosine A2A Antagonists in Animal Models of Parkinson’s Disease
Neuroprotection by Caffeine in a PD Model 153
Neuroprotection by Specific A2A Antagonists in PD Models 154
A Broader Neuroprotective Role for A2A Antagonists 155
Mechanisms of Protection by A2A Antagonist in PD Models 156
Significance for Parkinson’s Disease 159
References 159
INTRODUCTION
In Parkinson’s Disease (PD) the dopamine-containing brain cells (dopaminergic neurons) that originate in the substantia nigra and innervate the striatum gradually degenerate. Dopamine released from these nigrostriatal neurons serves to enhance normal motor activity. Accordingly, the progressive loss of dopamine that accompanies the loss of these neurons leads to an insidious and eventually profound slowing of movements (bradykinesia) except for the classic tremor at rest in many PD patients. Why central dopaminergic neurons selectively degenerate in typical PD remains a mystery. The recently intensified pursuit of environmental as well
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as genetic clues has yielded new insights into the causes and potential for improved treatment of this disabling disease. This chapter reviews the remarkably convergent lines of epidemiological and laboratory evidence that caffeine can protect dopaminergic neurons and may help prevent the development of this disease. The possibility that caffeine also produces a symptomatic motor benefit in PD has not been substantiated and is reviewed elsewhere (Fredholm et al., 1999; Schwarzschild et al., 2002).
