Chen Jiang-Fan, Sonsalla Patricia K, Pedata Felicita, Melani Alessia, Domenici Maria Rosaria, Popoli Patrizia, Geiger Jonathan, Lopes Luísa V, de Mendonça Alexandre
Department of Neurology, Boston University School of Medicine, 715 Albany Street, C329, Boston, MA 02118, USA.
Prog Neurobiol. 2007 Dec;83(5):310-31. doi: 10.1016/j.pneurobio.2007.09.002. Epub 2007 Sep 29.
This review summarizes recent developments that have contributed to understand how adenosine receptors, particularly A2A receptors, modulate brain injury in various animal models of neurological disorders, including Parkinson's disease (PD), stroke, Huntington's disease (HD), multiple sclerosis, Alzheimer's disease (AD) and HIV-associated dementia. It is clear that extracellular adenosine acting at adenosine receptors influences the functional outcome in a broad spectrum of brain injuries, indicating that A2A Rs may modulate some general cellular processes to affect neuronal cells death. Pharmacological, neurochemical and molecular/genetic approaches to the complex actions of A2A receptors in different cellular elements suggest that A2A receptor activation can be detrimental or protective after brain insults, depending on the nature of brain injury and associated pathological conditions. An interesting concept that emerges from these studies is A2A R's ability to fine tune neuronal and glial functions to produce neuroprotective effects. While the data presented here clearly highlight the complexity of using adenosinergic agents therapeutically in PD and other neurodegenerative disorders and point out many areas for further inquiry, they also confirm that adenosine receptor ligands, particularly A2A receptor ligands, have many promising characteristics that encourage the pursuit of their therapeutic potential.
本综述总结了近期的研究进展，这些进展有助于理解腺苷受体，尤其是A2A受体，在包括帕金森病（PD）、中风、亨廷顿舞蹈病（HD）、多发性硬化症、阿尔茨海默病（AD）和HIV相关痴呆在内的各种神经疾病动物模型中如何调节脑损伤。显然，作用于腺苷受体的细胞外腺苷会影响广泛脑损伤中的功能结局，这表明A2A受体可能调节一些一般细胞过程以影响神经元细胞死亡。针对A2A受体在不同细胞成分中的复杂作用所采用的药理学、神经化学和分子/遗传学方法表明，根据脑损伤的性质和相关病理状况，A2A受体激活在脑损伤后可能是有害的或具有保护作用。这些研究中出现的一个有趣概念是A2A受体能够微调神经元和胶质细胞功能以产生神经保护作用。虽然此处呈现的数据清楚地凸显了在帕金森病和其他神经退行性疾病中治疗性使用腺苷能药物的复杂性，并指出了许多有待进一步探究的领域，但这些数据也证实，腺苷受体配体，尤其是A2A受体配体，具有许多有前景的特性，这鼓励人们探索它们的治疗潜力。
