Schwarzschild Michael A, Xu Kui, Oztas Emin, Petzer Jacobus P, Castagnoli Kay, Castagnoli Neal, Chen Jiang-Fan
Department of Neurology, Massachusetts General Hospital, Boston, MA 02129, USA.
Neurology. 2003 Dec 9;61(11 Suppl 6):S55-61. doi: 10.1212/01.wnl.0000095214.53646.72.
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.
流行病学和实验室数据的显著趋同提出了一种可能性，即咖啡因通过防止黑质纹状体多巴胺能神经元的退化来降低患帕金森病（PD）的风险。作者回顾了咖啡因和更特异性的腺苷A2A受体拮抗剂在几种PD毒素模型中保护多巴胺能神经元的证据。其他研究表明，在中风、亨廷顿舞蹈病和阿尔茨海默病动物模型中，A2A受体失活具有保护作用，这表明A2A受体在神经元损伤和退化中发挥着更广泛的作用。虽然A2A受体导致神经元死亡的细胞和分子机制尚未明确，但已经出现了几种有趣的可能性。现在，初步临床数据证实了A2A受体阻断对帕金森病症状的改善作用，A2A拮抗剂具有互补性神经保护作用的前景增强了其在PD治疗中的潜力。
