Digicaylioglu Murat
Department of Neurosurgery, University of Texas Health Science Center, San Antonio, TX, USA.
Methods Mol Biol. 2013;982:175-86. doi: 10.1007/978-1-62703-308-4_11.
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.
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。