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: 10616815
• 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/10616815
• 关键词: 3-Dimensional; Acute; Adverse effects; Animal Model; Biomedical Research; Blood flow; Brain; Brain Injuries; Cause of Death; Cell Death; Cytotoxic agent; Excision; Exhibits; Foundations; Future; Galactosyltransferases; Genes; Grant; Hematopoietic; Human; Hypoxia; Impairment; In Vitro; Inflammation; Injury; Intervention; Ischemia; Ischemic Brain Injury; Ischemic Stroke; Mammalian Cell; Mediating; Middle Cerebral Artery Occlusion; Mus; Nervous System Physiology; Neurologic; Neurologic Effect; Neurological outcome; Neurons; Neuroprotective Agents; Obstruction; Pathway interactions; Persons; Pharmaceutical Preparations; 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; cardioprotection; cell injury; clinical practice; conditioning; disability; drug candidate; glycosylation; in vivo; innovation; molecular marker; mouse model; neurogenesis; neuroprotection; new therapeutic target; pharmacologic; prevent; protective effect; recombinant human erythropoietin; sialylation; 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。

项目成果

A Rapid Alkalinization Factor-like Peptide EaF82 Impairs Tapetum Degeneration during Pollen Development through Induced ATP Deficiency.

• DOI: 10.3390/cells12111542
• 发表时间: 2023-06-04
• 期刊: CELLS
• 影响因子: 6
• 作者: Hung, Chiu-Yueh;Kittur, Farooqahmed S.;Wharton, Keely N.;Umstead, Makendra L.;Burwell, D'Shawna B.;Thomas, Martinique;Qi, Qi;Zhang, Jianhui;Oldham, Carla E.;Burkey, Kent O.;Chen, Jianjun;Xie, Jiahua
• 通讯作者: Xie, Jiahua

An Effective Way of Producing Fully Assembled Antibody in Transgenic Tobacco Plants by Linking Heavy and Light Chains via a Self-Cleaving 2A Peptide.

• DOI: 10.3389/fpls.2018.01379
• 发表时间: 2018
• 期刊: Frontiers in plant science
• 影响因子: 5.6
• 作者: Lin Y;Hung CY;Bhattacharya C;Nichols S;Rahimuddin H;Kittur FS;Leung T;Xie J
• 通讯作者: Xie J

Asialo-rhuEPO as a Potential Neuroprotectant for Ischemic Stroke Treatment.

• DOI: 10.3390/ph16040610
• 发表时间: 2023-04-18
• 期刊: Pharmaceuticals (Basel, Switzerland)
• 作者: Kittur FS;Hung CY;Li PA;Sane DC;Xie J
• 通讯作者: Xie J

Glycoengineering tobacco plants to stably express recombinant human erythropoietin with different N-glycan profiles.

• DOI: 10.1016/j.ijbiomac.2020.04.199
• 发表时间: 2020-08-15
• 期刊: International journal of biological macromolecules
• 影响因子: 8.2
• 作者: Kittur FS;Hung CY;Zhu C;Shajahan A;Azadi P;Thomas MD;Pearce JL;Gruber C;Kallolimath S;Xie J
• 通讯作者: Xie J

Regulation of one-carbon metabolism may open new avenues to slow down the initiation and progression of Huntington's disease.

• DOI: 10.4103/1673-5374.371363
• 发表时间: 2023-11
• 期刊: Neural regeneration research
• 影响因子: 6.1
• 作者: Xie J;Kittur FS;Hung CY;Ding TT
• 通讯作者: Ding TT