Therapeutic implications of purinergic receptor P2X4 in ischemic stroke

总结： 中风仍然是美国残疾的主要原因。中风是一种异质性多因素 disorder.先前开发新疗法的尝试由于不完善的靶点验证而在临床上失败， 不切实际的治疗窗口和缺乏适合年龄的模型。因此，有机会和需要 来寻找治疗中风的新药物免疫细胞移动到大脑中的中风区域， 破坏。我们最近发现嘌呤能P2X4受体被腺苷过度刺激， 中风时垂死的脑细胞释放的三磷酸盐（ATP）。这种受体蛋白然后引起 免疫细胞，导致更严重的中风损伤。我们已经组装了必要的工具，如动物 缺乏P2X4受体以及选择性抑制该受体的阻断剂。该提案，利用这些新的 工具，旨在研究这种受体蛋白是否是开发治疗受试者的新靶点。 中风我们的初步数据表明，在中风急性期阻断或删除这种受体蛋白， 有利于然而，目前尚不清楚这种蛋白质是如何工作的，以及它的潜在副作用可能是什么。 解决这些问题是这里的总目标，应该确定追求新的 中风治疗

Summary: Stroke remains a leading cause of disability in the United States. Stroke is a heterogeneous multifactorial disorder. Prior attempts at developing new therapies have failed in clinics due to imperfect target validation, unrealistic therapeutic windows and lack of age appropriate models. Thus, there is an opportunity and a need to identify new medical treatment for stroke. The immune cells move to stroke area in the brain and contribute to damage. We have recently shown that the purinergic P2X4 receptor is excessively stimulated by adenosine triphosphate (ATP) released by dying brain cells during stroke. This receptor protein then causes activation of the immune cells and results in greater stroke injury. We have assembled the necessary tools such as animals lacking P2X4 receptors as well as blockers that selectively inhibit the receptor. The proposal, using these new tools, aims to investigate whether this receptor protein is a novel target to develop treatment for subjects with stroke. Our initial data suggest that blocking or deleting this receptor protein during the acute phase of stroke is beneficial. However, it is unknown how this protein works and what its potential adverse effects might be. Answering these questions is the overall goal here and should define the correct approach in pursuing a new stroke treatment