Senicapoc：将药物重新用于靶向中风中的小胶质细胞 K3.1。
Senicapoc: Repurposing a Drug to Target Microglia K3.1 in Stroke.
机构信息
Alentis Pharma LLC, 72 Hillside Avenue, Metuchen, NJ, 08840, USA.
Department of Neurology, School of Medicine, University of Washington, Seattle, WA, 98195, USA.
出版信息
Neurochem Res. 2017 Sep;42(9):2639-2645. doi: 10.1007/s11064-017-2223-y. Epub 2017 Mar 31.
Abstract
Stroke is the leading cause of serious long-term disability and the fifth leading cause of death in the United States. Treatment options for stroke are few in number and limited in efficacy. Neuroinflammation mediated by microglia and infiltrating peripheral immune cells is a major component of stroke pathophysiology. Interfering with the inflammation cascade after stroke holds the promise to modulate stroke outcome. The calcium activated potassium channel K3.1 is expressed selectively in the injured CNS by microglia. K3.1 function has been implicated in pro-inflammatory activation of microglia and there is recent literature suggesting that this channel is important in the pathophysiology of ischemia/reperfusion (stroke) related brain injury. Here we describe the potential of repurposing Senicapoc, a K3.1 inhibitor, to intervene in the inflammation cascade that follows ischemia/reperfusion.
摘要
中风是美国导致严重长期残疾和第五大死亡原因。中风的治疗选择很少，疗效有限。小胶质细胞和浸润的外周免疫细胞介导的神经炎症是中风病理生理学的主要组成部分。中风后干扰炎症级联反应有望调节中风的结果。钙激活钾通道 K3.1 由小胶质细胞选择性表达在受损的中枢神经系统中。K3.1 功能与小胶质细胞的促炎激活有关，最近有文献表明该通道在缺血/再灌注（中风）相关脑损伤的病理生理学中很重要。在这里，我们描述了重新利用 Senicapoc（一种 K3.1 抑制剂）来干预缺血/再灌注后炎症级联反应的潜力。
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Inhibition of the potassium channel K3.1 by senicapoc reverses tactile allodynia in rats with peripheral nerve injury.塞尼卡波对钾通道K3.1的抑制作用可逆转周围神经损伤大鼠的触觉异常性疼痛。
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Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke.小胶质细胞对脑损伤有保护作用，其选择性消除会导致中风后神经元网络活动失调。
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