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

植物产生的去唾液酸促红细胞生成素的体内神经保护特性和作用机制

基本信息

批准号：
10172032
负责人：
Jiahua Xie
金额：
$ 37万
依托单位：
NORTH CAROLINA CENTRAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10172032
关键词：
3-Dimensional Acute Adverse effects Animal Model Biomedical Research Blood flow Brain Brain Injuries Cause of Death Cell Death Cytotoxic agent Erythropoietin Excision Exhibits Foundations Future Galactosyltransferases Genes Grant Hematopoietic Human Hypoxia Impairment In Vitro Inflammation Injury Intervention Ischemia Ischemic Stroke Lead Mammalian Cell Mediating Middle Cerebral Artery Occlusion Mus Nervous System Physiology Neurologic Neurologic Effect Neurological outcome Neurons Neuroprotective Agents Obstruction Pathway interactions Pharmaceutical Preparations Pharmacology Plants Polysaccharides Procedures Process Property Recombinants Reperfusion Injury Reperfusion Therapy Reporting Research Activity Role Sialic Acids Signal Pathway Solid Stroke Structure Students Survival Rate System Testing Time Transgenic Plants Translating Underrepresented Minority aged angiogenesis base cardioprotection cell injury clinical practice conditioning disability drug candidate glycosylation in vivo innovation molecular marker mouse model neurogenesis neuroprotection new therapeutic target prevent protective effect recombinant human erythropoietin side effect stroke clinical trials success tissue repair training opportunity

项目摘要

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.

抽象的迫切需要开发神经保护药物来预防或/和保护神经元细胞脑部缺血/再灌注、缺氧或细胞毒性药物引起的损伤和死亡。植物- 基于表达系统可用于产生asialo-rhuEPO，一种非造血细胞缺乏唾液酸的重组人EPO衍生物，可用作神经保护剂用于预防和保护脑部免受缺血/再灌注损伤的药物。在我们之前的研究发现，植物产生的 asialo-rhuEPO (asialo-rhuEPOP) 不具有促红细胞生成作用，并且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。我们之前的研究为当前提出的方案奠定了基础研究活动。在此 SC1 续订申请中，我们建议延长 asialo-rhuEPOP 介导的对老年小鼠的神经保护研究，评估年轻小鼠和小鼠的长期神经学结果老年小鼠，进一步了解其神经保护机制。