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

• 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
• 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

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.

摘要 迫切需要开发神经保护药物来预防或/和保护神经细胞。 脑缺血/再灌流、缺氧或细胞毒性物质引起的损伤和死亡。植物- 基于表达系统的重组人促红细胞生成素可用于生产非造血药 不含唾液酸的重组人促红细胞生成素衍生物可用于神经保护 用于预防和保护脑缺血/再灌注损伤的药物。在我们之前的 研究发现，植物来源的asialo-rhuEPO(asialo-rhuEPOP)是非红系的， 在幼年小鼠大脑中动脉模型中显示出良好的神经保护作用 闭塞(MCAO)I/R损伤。我们之前的研究已经为目前提出的 研究活动。在这个SC1续订申请中，我们建议扩展asialo-rhuEPOP介导的 对老年小鼠的神经保护研究，评估年轻和年轻小鼠的长期神经结果 并进一步了解其神经保护机制。