Department of Medicine (Neurology), Duke University School of Medicine, Durham, NC 27710, USA.
Exp Neurol. 2013 Mar;241:67-74. doi: 10.1016/j.expneurol.2012.11.027. Epub 2012 Dec 6.
Growing clinical evidence implicates isoform-specific effects of apolipoprotein E (apoE) in reducing neuroinflammation and mediating adaptive responses following ischemic and traumatic brain injury. However, the intact apoE holoprotein does not cross the blood-brain barrier and thus has limited therapeutic potential. We have created a small peptide, COG1410 (acetyl-AS-Aib-LRKL-Aib-KRLL-amide), derived from the apoE receptor-binding region. COG1410 retains the anti-inflammatory and neuroprotective biological properties of the intact holoprotein and penetrates the blood-brain barrier. In the current study, we utilized a murine model of transient focal cerebral ischemia and reperfusion to demonstrate that intravenous (IV) administration of COG1410 reduces infarct volume and radiographic progression of infarct, and improves functional outcome as assessed by rotarod when delivered up to 4h after ischemia onset.
越来越多的临床证据表明载脂蛋白 E（apoE）的异构体特异性效应对减少神经炎症和介导缺血性和创伤性脑损伤后的适应性反应具有重要作用。然而，完整的 apoE 全蛋白不能穿过血脑屏障，因此治疗潜力有限。我们已经开发了一种小肽 COG1410（乙酰-AS-Aib-LRKL-Aib-KRLL-酰胺），它来源于 apoE 的受体结合区域。COG1410 保留了完整全蛋白的抗炎和神经保护的生物学特性，并能穿透血脑屏障。在本研究中，我们利用短暂性局灶性脑缺血再灌注的小鼠模型证明，在缺血发作后 4 小时内给予 COG1410 静脉注射可减少梗死体积和梗死的放射学进展，并改善旋转棒试验评估的功能结果。
