Asialo-rhuEPO as a Potential Neuroprotectant for Ischemic Stroke Treatment.
Asialo-rhuEPO as a Potential Neuroprotectant for Ischemic Stroke Treatment.
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DOI：
10.3390/ph16040610
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发表时间：
2023-04-18
期刊：
影响因子：
--
通讯作者：
Xie J
中科院分区：
文献类型：
--
作者：
Kittur FS;Hung CY;Li PA;Sane DC;Xie J
迫切需要神经保护性药物来保护大脑免受脑缺血和再灌注(I/R)损伤。哺乳动物细胞产生的重组人促红细胞生成素(RhuEPOM)在临床前研究中已被证明具有良好的神经保护功能，但其神经保护作用在临床试验中并不一致。RhuEPOM的临床失败被认为主要是由于其红系活性相关的副作用。为了开发其组织保护功能，已开发出各种仅具有组织保护功能的EPO衍生物。其中，sialo-rHuEPO缺乏末端唾液酸残基，具有神经保护作用，但不具有促红细胞生成作用。通过酶法去除rhuEPOM中唾液酸残基(asialo-rhuEPOE)或在糖工程转基因植物中表达人EPO基因(asialo-rhuEPOP)可制备assialo-rhuEPO。两种sialo-rHuEPO与rhuEPOM一样，通过调节脑I/R动物模型中的多个细胞通路，显示出良好的神经保护作用。本文综述了促红细胞生成素和重组人促红细胞生成素的结构和性质，总结了促红细胞生成素和重组人促红细胞生成素的神经保护研究进展，讨论了重组人促红细胞生成素治疗急性缺血性卒中临床失败的可能原因，并建议进一步开发促红细胞生成素作为治疗缺血性卒中的多模式神经保护剂。
Neuroprotective drugs to protect the brain against cerebral ischemia and reperfusion (I/R) injury are urgently needed. Mammalian cell-produced recombinant human erythropoietin (rhuEPOM) has been demonstrated to have excellent neuroprotective functions in preclinical studies, but its neuroprotective properties could not be consistently translated in clinical trials. The clinical failure of rhuEPOM was thought to be mainly due to its erythropoietic activity-associated side effects. To exploit its tissue-protective property, various EPO derivatives with tissue-protective function only have been developed. Among them, asialo-rhuEPO, lacking terminal sialic acid residues, was shown to be neuroprotective but non-erythropoietic. Asialo-rhuEPO can be prepared by enzymatic removal of sialic acid residues from rhuEPOM (asialo-rhuEPOE) or by expressing human EPO gene in glycoengineered transgenic plants (asialo-rhuEPOP). Both types of asialo-rhuEPO, like rhuEPOM, displayed excellent neuroprotective effects by regulating multiple cellular pathways in cerebral I/R animal models. In this review, we describe the structure and properties of EPO and asialo-rhuEPO, summarize the progress on neuroprotective studies of asialo-rhuEPO and rhuEPOM, discuss potential reasons for the clinical failure of rhuEPOM with acute ischemic stroke patients, and advocate future studies needed to develop asialo-rhuEPO as a multimodal neuroprotectant for ischemic stroke treatment.
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影响因子：
3.7
作者：
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期刊：
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影响因子：
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作者：
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发表时间：
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影响因子：
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