Neuroprotection by caffeine and more specific A2A receptor antagonists in animal models of Parkinson's disease.
A remarkable convergence of epidemiologic and laboratory data has raised the possibility that caffeine reduces the risk of developing Parkinson's disease (PD) by preventing the degeneration of nigrostriatal dopaminergic neurons. The authors review the evidence that caffeine and more specific antagonists of the adenosine A2A receptor protect dopaminergic neurons in several toxin models of PD. Other studies demonstrating protection by A2A receptor inactivation in animal models of stroke, Huntington's disease, and Alzheimer's disease suggest a more global role of A2A receptors in neuronal injury and degeneration. Although the cellular and molecular mechanisms by which A2A receptors contribute to neuronal death are not yet established, several intriguing possibilities have emerged. Now with preliminary clinical data substantiating the antiparkinsonian symptomatic benefit of A2A receptor blockade, the prospects for a complementary neuroprotective benefit have enhanced the therapeutic potential of A2A antagonists in PD.
Schwarzschild
Michael A
MA
Department of Neurology, Massachusetts General Hospital, Boston, MA 02129, USA. michaels@helix.mgh.harvard.edu
Xu
Kui
K
Oztas
Emin
E
Petzer
Jacobus P
JP
Castagnoli
Kay
K
Castagnoli
Neal
N
Chen
Jiang-Fan
JF
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002110:Caffeine / Q000627:therapeutic use*; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D051379:Mice; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D018696:Neuroprotective Agents; D002110:Caffeine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine