University of Medicine and Dentistry of New Jersey, Cancer Center, New Jersey NJ 07103, USA.
Expert Opin Ther Targets. 2013 Jun;17(6):707-20. doi: 10.1517/14728222.2013.780599. Epub 2013 Mar 20.
Since erythropoietin (EPO) and EPO receptor (EPOR) are expressed in the central nervous system (CNS) beyond hematopoietic system, EPO illustrates a robust biological function in maintaining neuronal survival and regulating neurogenesis and may play a crucial role in neurodegenerative diseases.
EPO is capable of modulating multiple cellular signal transduction pathways to promote neuronal survival and enhance the proliferation and differentiation of neuronal progenitor cells. Initially, EPO binds to EPOR to activate the Janus-tyrosine kinase 2 (Jak2) protein followed by modulation of protein kinase B (Akt), mammalian target of rapamycin, signal transducer and activators of transcription 5, mitogen-activated protein kinases, protein tyrosine phosphatases, Wnt1 and nuclear factor κB. As a result, EPO may actively prevent the progression of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis and motor neuron diseases.
Novel knowledge of the cell signaling pathways regulated by EPO in the CNS will allow us to establish the foundation for the development of therapeutic strategies against neurodegenerative diseases. Further investigation of the role of EPO in neurodegenerative diseases can not only formulate EPO as a therapeutic candidate, but also further identify novel therapeutic targets for these disorders.
由于促红细胞生成素（EPO）及其受体（EPOR）在造血系统以外的中枢神经系统（CNS）中表达，EPO 在维持神经元存活和调节神经发生方面表现出强大的生物学功能，并且可能在神经退行性疾病中发挥关键作用。
EPO 能够调节多种细胞信号转导途径，促进神经元存活，并增强神经元祖细胞的增殖和分化。最初，EPO 与 EPOR 结合以激活 Janus 酪氨酸激酶 2（Jak2）蛋白，随后调节蛋白激酶 B（Akt）、雷帕霉素哺乳动物靶标、信号转导和转录激活因子 5、丝裂原激活蛋白激酶、蛋白酪氨酸磷酸酶、Wnt1 和核因子 κB。因此，EPO 可能积极预防阿尔茨海默病、帕金森病、癫痫、多发性硬化症和运动神经元疾病等神经退行性疾病的进展。
对 EPO 在 CNS 中调节的细胞信号通路的新知识将为我们开发针对神经退行性疾病的治疗策略奠定基础。进一步研究 EPO 在神经退行性疾病中的作用不仅可以将 EPO 制定为治疗候选物，还可以进一步确定这些疾病的新治疗靶点。
