In Vivo Neuroprotective Properties and Action Mechanism(s) of Plant-produced Asialo-erythropoietin

摘要 迫切需要开发神经保护药物来预防或/和保护神经元细胞 由脑中的缺血/再灌注、缺氧或细胞毒性剂引起的损伤和死亡。植物- 的表达系统可用于生产脱唾液酸-rhuEPO，一种非造血细胞 缺乏唾液酸的重组人EPO衍生物，其可用作神经保护剂， 用于预防和保护缺血/再灌注损伤引起的脑损伤的试剂。在我们以前 研究中，我们发现植物产生的无唾液酸-rhuEPO（无唾液酸-rhuEPOP）是非红细胞生成的， 在年轻小鼠大脑中动脉模型中显示出优异的神经保护作用， 闭塞（MCAO）I/R损伤。我们以前的研究为目前提出的 研究活动。在此SC 1更新申请中，我们建议将无唾液酸-rhuEPOP介导的 对老年小鼠的神经保护研究，评估了年轻和 老年小鼠，并进一步了解其神经保护机制。

Abstract There is an acute need to develop neuroprotective drugs to prevent or/and protect neuronal cell damage and death caused by ischemia/reperfusion, hypoxia or cytotoxic agents in the brain. Plant- based expression system can be used to produce asialo-rhuEPO, a non-hematopoietic recombinant human EPO derivative lacking sialic acid, which could be used as a neuroprotective agent for preventing and protecting brain damage from ischemia/reperfusion injury. In our previous studies, we found that plant-produced asialo-rhuEPO (asialo-rhuEPOP) is non-erythropoietic and displays excellent neuroprotective effects in a young mouse model of middle cerebral artery occlusion (MCAO) I/R injury. Our previous studies have set the stage for the current proposed research activities. In this SC1 renewal application, we propose to extend asialo-rhuEPOP-mediated neuroprotection studies to aged mice, evaluate long-term neurological outcomes in both young and aged mice, and further understand its neuroprotective mechanisms.