Neuroprotective role of adenosine in the CNS.
Neuroprotective role of adenosine in the CNS.
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发表时间：
2002-07
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通讯作者：
J. Wardas
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作者：
J. Wardas
已经确定，在CNS中，内源性腺苷在神经变性中起关键作用。细胞外液中通常存在低纳摩尔浓度的腺苷，但在神经活动增强、缺氧或缺血期间其显著增加。在这些病理条件下，腺苷能传递增强剂，其通过抑制其降解（腺苷脱氨酶和激酶抑制剂）或阻止其转运来提高腺苷水平，提供针对缺血性或兴奋性毒性神经元损伤的保护。已知直接作用的腺苷A1受体激动剂介导神经保护，主要通过阻断Ca 2+内流，这导致在突触后水平抑制谷氨酸释放并降低其兴奋作用。最近的数据表明，腺苷A2 A受体的拮抗剂在局灶性和全脑缺血的动物模型中显著降低脑缺血损伤。此外，这些化合物减弱兴奋性氨基酸（EAA）诱导的神经元损失。腺苷A2 A受体拮抗剂的神经保护作用也显示在帕金森病的动物模型（MPTP，6-OHDA，甲基苯丙胺）。因此，它可能是建议，腺苷A2 A受体拮抗剂可能代表一种新的策略，在治疗方法的病理特征的急性或慢性神经退行性事件，因为他们不仅逆转运动障碍，但可以作为神经保护化合物，促进细胞存活。
It is well established that in the CNS, endogenous adenosine plays a pivotal role in neurodegeneration. A low, nanomolar concentration of adenosine is normally present in the extracellular fluid, but it increases dramatically during enhanced nerve activity, hypoxia or ischemia. In these pathological conditions, adenosinergic transmission-potentiating agents, which elevate adenosine level by either inhibiting its degradation (adenosine deaminase and kinase inhibitors) or preventing its transport, offer protection against ischemic or excitotoxic neuronal damage. The directly acting adenosine A1 receptor agonists are known to mediate neuroprotection, mostly by the blockade of Ca2+ influx, which results in the inhibition of glutamate release and reduction of its excitatory effects at a postsynaptic level. More recent data have shown that antagonists of adenosine A2A receptors markedly reduce cerebral ischemic damage in animal models of focal and global ischemia. Moreover, these compounds attenuate the neuronal loss induced by excitatory amino acids (EAA). A neuroprotective effect of adenosine A2A receptor antagonists was also shown in animal models of Parkinson's disease (MPTP, 6-OHDA, methamphetamine). Hence, it might be suggested that adenosine A2A receptor antagonists may represent a novel strategy in the therapeutic approach to pathologies characterized by acute or chronic neurodegenerative events, since they not only reverse motor impairment but can act as neuroprotective compunds by promoting cell survival.