摘要
背景:外泌体是一种纳米级微型囊泡,可自由透过血脑屏障,在维持内环境稳定、进行细胞间通讯、调节免疫应答等方面有重要价值。间充质干细胞作为分泌外泌体能力最强的细胞,具有便于采集、免疫排斥小、伦理反应弱等优点,并且间充质干细胞源性外泌体有助于改善受损的神经系统功能,抑制多巴胺能神经元凋亡,被认为是治疗帕金森病的一种很有前途的治疗工具。目的:综述外泌体在帕金森病发病机制中的作用、作为诊断的生物标志物、药物递送载体以及间充质干细胞源性外泌体在帕金森病作用机制中的研究进展。方法:以“exosomes,mesenchymal stem cells,Parkinson disease”为英文检索词,以“外泌体,间充质干细胞,帕金森病”为中文检索词。检索自建库至2021年5月收录在中国知网与PubMed数据库的相关文献,检索语种为中文和英文,依据纳入和排除标准,最终纳入相关文献117篇。结果与结论:①概述了外泌体的定义、来源、组成及功能;间充质干细胞的发现、定义、作用机制及应用。②总结了α-突触核蛋白的聚集可引起病理学扩散,而从外泌体中发现了α-突触核蛋白,这可能是α-突触核蛋白在细胞间传播的可能分子机制;α-突触核蛋白可以激活帕金森病中的小胶质细胞,引起炎症级联反应,诱导神经炎和多巴胺神经元变性;外泌体miRNA可以诱导靶细胞遗传程序发生变化,上述发病机制促进了帕金森病进程。③总结了外泌体作为诊断的生物标志物、药物递送载体的应用,并且总结了间充质干细胞源性外泌体在帕金森病中的作用主要表现在抑制炎症反应、调节基因表达、抑制多巴胺神经元凋亡,从而发挥神经保护作用,增加了多巴胺的释放。④总结发现间充质干细胞源性外泌体在帕金森病的诊治中有广阔前景,值得进一步深入研究。
BACKGROUND:Exosomes are nano-scale microvesicles that can freely penetrate the blood-brain barrier and are of great values in maintaining the stability of the internal environment,communicating between cells,and regulating immune responses.Mesenchymal stem cells,as the cells with the strongest ability to secrete exosomes,have the advantages of easy collection,low immune rejection,and weak ethical response,and mesenchymal stem cell-derived exosomes can help improve damaged nervous system functions.Inhibiting the apoptosis of dopaminergic neurons is considered to be a promising therapeutic tool for the treatment of Parkinson’s disease.OBJECTIVE:To review the role of exosomes in the pathogenesis of Parkinson’s disease,as diagnostic biomarkers,drug delivery vehicles,and the research progress of mesenchymal stem cell-derived exosomes in the mechanism of Parkinson’s disease.METHODS:“Exosomes,mesenchymal stem cells,Parkinson disease”were used as the Chinese and English search terms.Relevant articles were searched in CNKI and PubMed from inception to May 2021.The search languages were Chinese and English.According to the inclusion and exclusion criteria,117 relevant articles were finally included.RESULTS AND CONCLUSION:(1)The definition,source,composition,and function of exosomes,the discovery,definition,mechanism and application of mesenchymal stem cells were summarized.(2)It is concluded that the aggregation ofα-synuclein can cause pathological spread,andα-synuclein is found in exosomes,which may be a possible molecular mechanism of the spread ofα-synuclein between cells.α-Synuclein can activate microglia in Parkinson’s disease,cause an inflammatory cascade,induce neuritis and dopamine neuron degeneration.Exosomal miRNA can induce changes in the genetic program of target cells.The above-mentioned pathogenesis promotes the progression of Parkinson’s disease.(3)The application of exosomes as diagnostic biomarkers and drug delivery vehicles is summarized.The role of mesenchymal stem cell-derived exosomes in Parkinson’s disease was summarized,mainly in inhibiting inflammation,regulating gene expression,inhibiting dopamine neuron apoptosis,thereby exerting a neuroprotective effect and increasing the release of dopamine.(4)It is found that mesenchymal stem cell-derived exosomes have broad prospects in the diagnosis and treatment of Parkinson’s disease,and are worthy of further in-depth study.
作者
卫宇帆
樊飞燕
李双利
张运克
Wei Yufan;Fan Feiyan;Li Shuangli;Zhang Yunke(Henan University of Chinese Medicine,Zhengzhou 450046,Henan Province,China;First Affiliated Hospital,Henan University of Chinese Medicine,Zhengzhou 450000,Henan Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2022年第25期4076-4083,共8页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金(81974564),项目负责人:张运克
河南省科技创新杰出人才项目(2018JR0006),项目负责人:张运克。
