Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
Health Clinical Laboratories, Health BioMed Co., Ltd. Ningbo, Zhejiang, China.
Brain Res. 2022 Sep 1;1790:147978. doi: 10.1016/j.brainres.2022.147978. Epub 2022 Jun 8.
Parkinson's disease (PD) is a common neurodegenerative disease. The main pathological changes are the loss of dopaminergic neurons and the formation of Lewy bodies. There is still no effective cure for PD, and cell replacement therapy has entered a bottleneck period due to tumorigenicity and rejection. Therefore, stem cell secretome has received widespread attention. However, the exploration of the secretome components of neural stem cells (NSCs) is still in its infancy. In this study, 6-hydroxydopamine (6-OHDA) was used to establish a PD rat model in vito and the PC12 cell-damaged model in vitro. The results indicated that the injection of neural stem cell-conditioned medium (NSC-CM) into the striatum and substantia nigra could improve the motor and non-motor deficits of PD rats and rescue the loss of dopaminergic neurons. In addition, NSC-CM alleviated 6-OHDA-induced apoptosis of PC12 cells, reduced the level of oxidative stress, and improved mitochondrial dysfunction in vitro. Parkinson disease protein 7 (Park7) was found in NSC-CM by Liquid chromatography-tandem mass spectrometry (LC-MS/MS), and it may be related to the protective effect of NSC-CM on 6-OHDA-injured neurons through Sirt1 pathway. In conclusion, NSC secretome might provide new ideas for the treatment of PD.
帕金森病(PD)是一种常见的神经退行性疾病。主要的病理变化是多巴胺能神经元的丧失和路易体的形成。目前还没有有效的 PD 治疗方法,由于致瘤性和排斥反应,细胞替代疗法已进入瓶颈期。因此,干细胞分泌组受到了广泛关注。然而,神经干细胞(NSCs)分泌组成分的探索仍处于起步阶段。在这项研究中,我们使用 6-羟基多巴胺(6-OHDA)在体内建立 PD 大鼠模型和体外 PC12 细胞损伤模型。结果表明,将神经干细胞条件培养基(NSC-CM)注射到纹状体和黑质可以改善 PD 大鼠的运动和非运动缺陷,并挽救多巴胺能神经元的丧失。此外,NSC-CM 减轻了 6-OHDA 诱导的 PC12 细胞凋亡,降低了氧化应激水平,并改善了体外的线粒体功能障碍。通过液相色谱-串联质谱(LC-MS/MS)在 NSC-CM 中发现了帕金森病蛋白 7(Park7),它可能通过 Sirt1 通路与 NSC-CM 对 6-OHDA 损伤神经元的保护作用有关。总之,NSC 分泌组可能为 PD 的治疗提供新的思路。