Neural stem cell secretome exerts a protective effect on damaged neuron mitochondria in Parkinson's disease model

• Stereotactic brain injection of concentrated neural stem cell-conditioned medium (NSC-CM) improves motor and nonmotor dysfunction and reduces dopaminergic neuron loss in Parkinson's disease (PD) rats. • NSC-CM ameliorates mitochondrial dysfunction, oxidative stress, and apoptosis in 6-hydroxydopamine (6-OHDA)-injured PC12 cells, might through the Sirtuin1 (Sirt1) pathway in vitro . • Through Liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection and bioinformatics analysis, the protective effect of NSC-CM on damaged neurons in PD model may be related to Parkinson disease protein 7 (Park7) in the secretome of neural stem cells. 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.