Schneider Armin, Kuhn Hans-Georg, Schäbitz Wolf-Rüdigger
Axaron Bioscience AG, Heidelberg, Germany.
Cell Cycle. 2005 Dec;4(12):1753-7. doi: 10.4161/cc.4.12.2213. Epub 2005 Dec 27.
G-CSF (Granulocyte-colony stimulating factor) is a hematopoietic growth factor that has been known for 20 years, and has been named for its role in the proliferation and differentiation of cells of the myeloic lineage. We have uncovered a novel spectrum of activities of G-CSF in the central nervous system. G-CSF and its receptor are expressed by neurons in many brain regions, and are upregulated upon experimental stroke. In neurons, G-CSF acts anti-apoptotically by activating several protective pathways. In vivo, G-CSF decreases infarct volumes in acute stroke models in rodents. Moreover, G-CSF stimulates neuronal differentiation of adult neural stem cells in the brain, and improves long-term recovery in more chronic stroke models. Thus, G-CSF is a novel neurotrophic factor, and a highly attractive candidate for the treatment of neurodegenerative conditions. Here we discuss this new property of G-CSF in contrast to its known functions in the hematopoietic system, summarize data from other groups on G-CSF's actions in cerebral ischemia, compare G-CSF to Erythropoietin (EPO) in the CNS, and highlight clinical implications.
粒细胞集落刺激因子(G-CSF)是一种已被熟知20年的造血生长因子,因其在髓系谱系细胞增殖和分化中的作用而得名。我们发现了G-CSF在中枢神经系统中的一系列新活性。G-CSF及其受体在许多脑区的神经元中表达,并在实验性中风后上调。在神经元中,G-CSF通过激活多种保护途径发挥抗凋亡作用。在体内,G-CSF可减少啮齿动物急性中风模型中的梗死体积。此外,G-CSF可刺激大脑中成年神经干细胞的神经元分化,并改善更慢性中风模型中的长期恢复情况。因此,G-CSF是一种新型神经营养因子,是治疗神经退行性疾病极具吸引力的候选药物。在此,我们将讨论G-CSF的这一新特性,并与其在造血系统中的已知功能进行对比,总结其他研究小组关于G-CSF在脑缺血中作用的数据,将G-CSF与中枢神经系统中的促红细胞生成素(EPO)进行比较,并强调其临床意义。