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Therapeutic potential of erythropoietin and its structural or functional variants in the nervous system.
Neurotherapeutics ( IF 5.7 ) Pub Date : 2008 , DOI: 10.1016/j.nurt.2008.10.041
Anna-Leena Sirén 1 , Theresa Fasshauer , Claudia Bartels , Hannelore Ehrenreich
Affiliation  

The growth factor erythropoietin (EPO) and erythropoietin receptors (EPOR) are expressed in the nervous system. Neuronal expression of EPO and EPOR peaks during brain development and is upregulated in the adult brain after injury. Peripherally administered EPO, and at least some of its variants, cross the blood-brain barrier, stimulate neurogenesis, neuronal differentiation, and activate brain neurotrophic, anti-apoptotic, anti-oxidant and anti-inflammatory signaling. These mechanisms underlie their tissue protective effects in nervous system disorders. As the tissue protective functions of EPO can be separated from its stimulatory action on hematopoiesis, novel EPO derivatives and mimetics, such as asialo-EPO and carbamoylated EPO have been developed. While the therapeutic potential of the novel EPO derivatives continues to be characterized in preclinical studies, the experimental findings in support for the use of recombinant human (rh)EPO in human brain disease have already been translated to clinical studies in acute ischemic stroke, chronic schizophrenia, and chronic progressive multiple sclerosis. In this review article, we assess the studies on EPO and, in particular, on its structural or functional variants in experimental models of nervous system disorders, and we provide a short overview of the completed and ongoing clinical studies testing EPO as neuroprotective/neuroregenerative treatment option in neuropsychiatric disease.

中文翻译:

促红细胞生成素及其在神经系统中的结构或功能变体的治疗潜力。

生长因子促红细胞生成素 (EPO) 和促红细胞生成素受体 (EPOR) 在神经系统中表达。EPO 和 EPOR 的神经元表达在大脑发育过程中达到峰值,并在受伤后在成人大脑中上调。外周给药的 EPO 及其至少一些变体可穿过血脑屏障,刺激神经发生、神经元分化,并激活脑神经营养、抗凋亡、抗氧化和抗炎信号。这些机制是它们在神经系统疾病中的组织保护作用的基础。由于 EPO 的组织保护功能与其对造血的刺激作用可以分开,因此开发了新型 EPO 衍生物和模拟物,例如去唾液酸-EPO 和氨基甲酰化 EPO。虽然新型 EPO 衍生物的治疗潜力继续在临床前研究中得到表征,但支持在人脑疾病中使用重组人 (rh) EPO 的实验结果已经转化为急性缺血性中风、慢性精神分裂症的临床研究和慢性进行性多发性硬化症。在这篇综述文章中,我们评估了关于 EPO 的研究,特别是关于它在神经系统疾病实验模型中的结构或功能变异,我们简要概述了已完成和正在进行的临床研究,将 EPO 测试为神经保护/神经再生治疗神经精神疾病的选择。支持在人脑疾病中使用重组人 (rh) EPO 的实验结果已经转化为急性缺血性中风、慢性精神分裂症和慢性进行性多发性硬化症的临床研究。在这篇综述文章中,我们评估了关于 EPO 的研究,特别是关于它在神经系统疾病实验模型中的结构或功能变异,我们简要概述了已完成和正在进行的临床研究,将 EPO 测试为神经保护/神经再生治疗神经精神疾病的选择。支持在人脑疾病中使用重组人 (rh) EPO 的实验结果已经转化为急性缺血性中风、慢性精神分裂症和慢性进行性多发性硬化症的临床研究。在这篇综述文章中,我们评估了关于 EPO 的研究,特别是关于它在神经系统疾病实验模型中的结构或功能变异,我们简要概述了已完成和正在进行的临床研究,将 EPO 测试为神经保护/神经再生治疗神经精神疾病的选择。
更新日期:2020-09-23
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