Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia.
Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
PLoS One. 2021 Oct 11;16(10):e0258289. doi: 10.1371/journal.pone.0258289. eCollection 2021.
The glial cell line-derived neurotrophic factor (GDNF) is involved in the survival of dopaminergic neurons. Besides, GDNF can also induce axonal growth and creation of new functional synapses. GDNF potential is promising for translation to treat diseases associated with neuronal death: neurodegenerative disorders, ischemic stroke, and cerebral or spinal cord damages. Unproductive clinical trials of GDNF for Parkinson's disease treatment have induced to study this failure. A reason could be due to irrelevant producer cells that cannot perform the required post-translational modifications. The biological activity of recombinant mGDNF produced by E. coli have been compared with mGDNF produced by human cells HEK293. mGDNF variants were tested with PC12 cells, rat embryonic spinal ganglion cells, and SH-SY5Y human neuroblastoma cells in vitro as well as with a mouse model of the Parkinson's disease in vivo. Both in vitro and in vivo the best neuro-inductive ability belongs to mGDNF produced by HEK293 cells. Keywords: GDNF, neural differentiation, bacterial and mammalian expression systems, cell cultures, model of Parkinson's disease.
胶质细胞源性神经营养因子(GDNF)参与多巴胺能神经元的存活。此外,GDNF 还可以诱导轴突生长和新功能性突触的形成。GDNF 具有转化为治疗与神经元死亡相关疾病的潜力:神经退行性疾病、缺血性中风以及脑或脊髓损伤。GDNF 治疗帕金森病的临床试验没有成效,促使人们对这一失败进行研究。原因之一可能是由于相关的生产细胞不能进行所需的翻译后修饰。已经比较了大肠杆菌产生的重组 mGDNF 与人类细胞 HEK293 产生的 mGDNF 的生物学活性。在体外,使用 PC12 细胞、大鼠胚胎脊髓神经节细胞和 SH-SY5Y 人神经母细胞瘤细胞以及体内帕金森病小鼠模型对 mGDNF 变体进行了测试。无论是在体外还是体内,HEK293 细胞产生的 mGDNF 具有最佳的神经诱导能力。关键词:GDNF、神经分化、细菌和哺乳动物表达系统、细胞培养、帕金森病模型。