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解析促红细胞生成素在神经元细胞中的细胞内信号传导。

Deciphering the intracellular signaling of erythropoietin in neuronal cells.

作者信息

Digicaylioglu Murat

机构信息

Department of Neurosurgery, University of Texas Health Science Center, San Antonio, TX, USA.

出版信息

Methods Mol Biol. 2013;982:175-86. doi: 10.1007/978-1-62703-308-4_11.

DOI:10.1007/978-1-62703-308-4_11
PMID:23456869
Abstract

The search for potential drugs to treat neurodegenerative diseases has been intense in the last two decades. Among many candidates, erythropoietin (EPO) was identified as a potent protectant of neurons suffering from various adverse conditions. A wide array of literature indicates that endogenous or exogenous recombinant human erythropoietin and its variants activate cell signaling that initiates survival-promoting events in neurons and neuronal cells. This chapter gives an overview of the pro-survival signaling induced by endogenous and exogenous erythropoietin in vitro and in vivo and provides methods to further investigate the intracellular signaling. It is important to know that EPO is neuroprotective, but it will greatly enhance our chances to establish EPO as a new drug candidate if we know how EPO protects neurons.The descriptions below summarize our current knowledge in non-neuronal and neuronal signaling pathways induced by EPO. The signaling pathways involved in EPO are multiple; some are well known whereas others are still under intense investigation and few are observed in very specific cell types. It is important to note that neuronal signaling events triggered by EPO are still incomplete and require further research. Therefore, excellent review articles that explore specific EPO-signaling events are referenced.

摘要

在过去二十年中,对治疗神经退行性疾病的潜在药物的研究一直十分活跃。在众多候选药物中,促红细胞生成素(EPO)被确定为对遭受各种不利条件的神经元具有强大保护作用的物质。大量文献表明,内源性或外源性重组人促红细胞生成素及其变体可激活细胞信号传导,从而启动神经元和神经细胞中的促存活事件。本章概述了内源性和外源性促红细胞生成素在体外和体内诱导的促存活信号传导,并提供了进一步研究细胞内信号传导的方法。了解促红细胞生成素具有神经保护作用固然重要,但如果我们知道促红细胞生成素如何保护神经元,将极大地增加我们将其确立为新候选药物的机会。以下描述总结了我们目前对促红细胞生成素诱导的非神经元和神经元信号通路的认识。促红细胞生成素涉及的信号通路有多种;有些是众所周知的,而其他的仍在深入研究中,并且只有极少数在非常特定的细胞类型中被观察到。需要注意的是,促红细胞生成素引发的神经元信号事件仍不完整,需要进一步研究。因此,本文引用了探讨特定促红细胞生成素信号事件的优秀综述文章。

相似文献

1
Deciphering the intracellular signaling of erythropoietin in neuronal cells.解析促红细胞生成素在神经元细胞中的细胞内信号传导。
Methods Mol Biol. 2013;982:175-86. doi: 10.1007/978-1-62703-308-4_11.
2
Targeting erythropoietin for chronic neurodegenerative diseases.针对慢性神经退行性疾病的促红细胞生成素。
Expert Opin Ther Targets. 2013 Jun;17(6):707-20. doi: 10.1517/14728222.2013.780599. Epub 2013 Mar 20.
3
Neuroprotective effects of erythropoietin in the rat hippocampus after pilocarpine-induced status epilepticus.匹罗卡品诱导癫痫持续状态后促红细胞生成素对大鼠海马的神经保护作用。
Neurobiol Dis. 2007 Feb;25(2):412-26. doi: 10.1016/j.nbd.2006.10.009. Epub 2006 Dec 12.
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Protective action of erythropoietin on neuronal damage induced by activated microglia.促红细胞生成素对激活小胶质细胞诱导的神经元损伤的保护作用。
FEBS J. 2013 Apr;280(7):1630-42. doi: 10.1111/febs.12172. Epub 2013 Mar 1.
5
A "classical" homodimeric erythropoietin receptor is essential for the antiapoptotic effects of erythropoietin on differentiated neuroblastoma SH-SY5Y and pheochromocytoma PC-12 cells.一种“经典”的同二聚体促红细胞生成素受体对于促红细胞生成素对分化的神经母细胞瘤SH-SY5Y细胞和嗜铬细胞瘤PC-12细胞的抗凋亡作用至关重要。
Cell Signal. 2007 Mar;19(3):634-45. doi: 10.1016/j.cellsig.2006.08.014. Epub 2006 Aug 30.
6
Erythropoietin receptor expression is concordant with erythropoietin but not with common beta chain expression in the rat brain throughout the life span.在大鼠整个生命周期中,促红细胞生成素受体的表达与促红细胞生成素一致,但与大鼠脑中常见的β链表达不一致。
J Comp Neurol. 2009 Jun 1;514(4):403-14. doi: 10.1002/cne.22020.
7
L-DOPA neurotoxicity is prevented by neuroprotective effects of erythropoietin.促红细胞生成素的神经保护作用可预防 L-DOPA 神经毒性。
Neurotoxicology. 2011 Dec;32(6):879-87. doi: 10.1016/j.neuro.2011.05.009. Epub 2011 Jun 7.
8
β Common receptor integrates the erythropoietin signaling in activation of endothelial nitric oxide synthase.β 共同受体整合了促红细胞生成素信号在内皮型一氧化氮合酶的激活中。
J Cell Physiol. 2011 Dec;226(12):3330-9. doi: 10.1002/jcp.22678.
9
ERK- and Akt-dependent neuroprotection by erythropoietin (EPO) against glyoxal-AGEs via modulation of Bcl-xL, Bax, and BAD.促红细胞生成素(EPO)通过调节 Bcl-xL、Bax 和 BAD 对糖基化终产物(AGEs)的 ERK 和 Akt 依赖性神经保护作用。
Invest Ophthalmol Vis Sci. 2010 Jan;51(1):35-46. doi: 10.1167/iovs.09-3544. Epub 2009 Jul 23.
10
Erythropoietin prevents early and late neuronal demise through modulation of Akt1 and induction of caspase 1, 3, and 8.促红细胞生成素通过调节Akt1以及诱导胱天蛋白酶1、3和8,预防早期和晚期神经元死亡。
J Neurosci Res. 2003 Mar 1;71(5):659-69. doi: 10.1002/jnr.10528.