Key Laboratory for Ethnomedicine for Ministry of Education, Center on Translational Neuroscience, College of Life and Environmental Sciences, School of Pharmacy, Minzu University of China, Beijing, China.
Oxid Med Cell Longev. 2020 Nov 26;2020:3807476. doi: 10.1155/2020/3807476. eCollection 2020.
Parkinson's disease (PD) is a common and complex neurodegenerative disease; the pathogenesis of which is still uncertain. Exosomes, nanosized extracellular vesicles, have been suggested to participate in the pathogenesis of PD, but their role is unknown. Here, a metabolomic analysis of serum and brain exosomes showed differentially expressed metabolites between 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride- (MPTP-) induced PD mice and control mice, such as oxidized lipids, vitamins, and cholesterol. These metabolites were enriched in coenzyme, nicotinamide, and amino acid pathways related to PD, and they could be served as preclinical biomarkers. We further found that blood-derived exosomes from healthy volunteers alleviated impaired motor coordination in MPTP-treated mice. Results from immunohistochemistry and western blotting indicated that the loss of dopaminergic neurons in substantia nigra and striatum of PD model mice was rescued by the exosome treatment. The exosome treatment also restored the homeostasis of oxidative stress, neuroinflammation, and cell apoptosis in the model mice. These results suggest that exosomes are important mediators for PD pathogenesis, and exosomes are promising targets for the diagnosis and treatment of PD.
帕金森病(PD)是一种常见且复杂的神经退行性疾病,其发病机制尚不清楚。外泌体,纳米大小的细胞外囊泡,被认为参与了 PD 的发病机制,但它们的作用尚不清楚。在这里,对血清和脑外泌体的代谢组学分析显示,1-甲基-4-苯基-1,2,3,6-四氢吡啶盐酸盐(MPTP)诱导的 PD 小鼠与对照小鼠之间存在差异表达的代谢物,如氧化脂质、维生素和胆固醇。这些代谢物在与 PD 相关的辅酶、烟酰胺和氨基酸途径中富集,它们可以作为临床前生物标志物。我们进一步发现,来自健康志愿者的血液衍生的外泌体缓解了 MPTP 处理的小鼠运动协调受损。免疫组织化学和 Western blot 结果表明,外泌体处理挽救了 PD 模型小鼠黑质和纹状体多巴胺能神经元的丢失。外泌体处理还恢复了模型小鼠氧化应激、神经炎症和细胞凋亡的平衡。这些结果表明,外泌体是 PD 发病机制的重要介质,外泌体是 PD 的诊断和治疗的有希望的靶点。