Adenosine kinase is a new therapeutic target to prevent ischemic neuronal death.
Adenosine kinase is a new therapeutic target to prevent ischemic neuronal death.
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发表时间：
2010
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通讯作者：
D. Boison;H. Shen
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作者：
D. Boison;H. Shen
大脑已经进化出几种内源性机制来保护自己免受中风的有害后果。这些内源性神经保护系统中的一个以嘌呤核糖核苷腺苷为中心，其在脑内发挥有效的神经保护功能。治疗性中风研究的一个主要目标是探索和利用这种内源性神经保护机制进行治疗。本文综述了研究腺苷系统在中风中作用的分子方法，并强调了旨在增加腺苷能功能的创新治疗方法。新的研究数据表明，主要的腺苷调节酶腺苷激酶（ADK）在决定大脑对缺血性损伤的易感性方面起着重要作用。因此，内源性ADK在中风后迅速下调，这可能是一种内源性神经保护机制，旨在提高脑中腺苷的环境水平。相反，ADK在脑中的转基因过表达使脑更容易受到中风诱导的神经元细胞损失。在本综述中，我们将首先总结腺苷代谢在缺血性脑损伤中的生理作用。接下来，我们将强调ADK在确定脑对缺血性损伤的易感性中的关键作用，最后我们将讨论腺苷增强在中风中提供神经保护的潜在治疗应用。
The brain has evolved several endogenous mechanisms to protect itself from the deleterious consequences of stroke. One of those endogenous neuroprotective systems is centered on the purine ribonucleoside adenosine, which exerts potent neuroprotective functions within the brain. One major goal in therapeutic stroke research is to explore and utilize such endogenous neuroprotective mechanisms therapeutically. This review illustrates molecular approaches to study the role of the adenosine system within the context of stroke and highlights innovative therapeutic approaches aimed at increasing adenosinergic function. New research data suggest that the major adenosine regulating enzyme adenosine kinase (ADK) plays a prominent role in determining the brain's susceptibility to ischemic injury. Thus, endogenous ADK is rapidly downregulated following a stroke, possibly an endogenous neuroprotective mechanism aimed at raising ambient levels of adenosine in brain. Conversely, transgenic overexpression of ADK in brain renders the brain more susceptible to stroke-induced neuronal cell loss. In the present review we will first summarize the physiological role of adenosine metabolism within the context of ischemic brain injury. Next, we will highlight the key role of ADK in determining the brain's susceptibility to ischemic injury, and finally we will discuss potential therapeutic applications of adenosine augmentation to provide neuroprotection in stroke.