外泌体介导细胞通讯:帕金森病的潜在生物标志物分析

Exosome-mediated cellular communication:a potential biomarker for Parkinson’s disease

背景:帕金森病是全球第二大神经退行性疾病,其运动症状和非运动症状都严重影响患者日常生活,最近研究发现外泌体及其携带的物质参与帕金森病病理发生发展,且还介导细胞通讯可作为帕金森病的潜在生物标志物。目的:探讨外泌体介导细胞通讯作为帕金森病的潜在生物标志物的类型及其发生作用的机制,用以寻找新的早期诊疗靶点,以期减缓帕金森病的发病进程并为其诊疗提供新思路。方法:应用计算机检索1987年1月至2022年8月PubMed、中国知网、万方数据、维普、Web of Science、EMBASE、Cochrane、EBSCO和SinoMed数据库收录的相关文献,最终纳入76篇英文文献和2篇中文文献进行归纳分析。结果与结论:(1)外泌体通过胞吞胞吐膜融合方式输送物质至受体细胞或膜表面携带信号因子,释放在细胞间隙等方式在细胞间通讯进行物质交换。(2)外泌体可通过介导细胞间通讯和信息交流以及物质运输参与帕金森病的病理进展,因此其可作为帕金森病的早期生物标志物,协助提供新的诊疗靶点,并可作为将来帕金森病的诊疗载体。(3)外泌体通过细胞间传递和物质运输扩散介导参与帕金森病病理发展机制,其主要生物标志物与病理作用途径的关系为:外泌体α突触核蛋白介导神经毒性、神经炎症、氧化应激及细胞自噬等过程,外泌体微小RNA可以靶向帕金森病相关基因并参与氧化应激,外泌体DJ-1蛋白调控细胞的氧化应激水平并影响细胞毒性,外泌体富含亮氨酸的重复激酶2介导路易体形成和堆积造成神经毒性,以上外泌体及其携带物质均可作为帕金森病的早期生物标志物。(4)目前外泌体的帕金森病生物标志物相关研究较少,但其中最具代表性和应用最多的是外泌体α突触核蛋白,由于外泌体微小RNA种类多数量大,在帕金森病中表达和作用不尽相同,近两年成为了研究热点。(5)目前相关研究缺少相应的临床验证,因此可做为未来研究方向,研究前景广阔,因此更需深入验证和研究更多的潜在生物标志物及其作用机制,为帕金森病的早期诊断提供诊疗新靶点。(6)外泌体在临床诊断帕金森病中的应用仍有很大的研究空间和发展前景,基于临床试验开展外泌体介导细胞通讯在帕金森病诊治中的应用是未来研究的重点和亟待突破点。

BACKGROUND:Parkinson’s disease is the second largest neurodegenerative disease in the world.Both motor symptoms and non-motor symptoms seriously affect the daily life of patients.Recent studies have found that exosomes and the substances they carry are involved in the pathogenesis of Parkinson’s disease.It also mediates cell communication and can be used as a potential biomarker for Parkinson’s disease.OBJECTIVE:To explore the type and mechanism of exosome-mediated cell communication as a potential biomarker of Parkinson’s disease,to find a new target for early diagnosis and treatment,to slow down the pathogenesis of Parkinson’s disease and provide new ideas for its diagnosis and treatment.METHODS:The related articles included in PubMed,CNKI,WanFang,VIP,Web of Science,EMBASE,Cochrane,EBSCO,and SinoMed databases from January 1987 to August 2022 were searched by computer,and 76 English and 2 Chinese articles were finally included for inductive analysis.RESULTS AND CONCLUSION:(1)The exosomes transport substances to recipient cells or membrane surface through endocytosis and exocytosis membrane fusion to carry signaling factors and release them in the intercellular space and other means for the exchange of substances between cells.(2)Exosomes can participate in the pathological progress of Parkinson’s disease by mediating intercellular communication and information exchange and material transport,so they can be used as early biomarkers of Parkinson’s disease,help provide new diagnosis and treatment targets,and can be used as a diagnostic carrier for Parkinson’s disease in the future.(3)The exosomes participate in mechanism of the pathological development of Parkinson’s disease through intercellular transmission and substance transport and diffusion.The relationship between its main biomarkers and pathologic pathways is that in neurotoxicity,neuroinflammation,oxidative stress,autophagy and other processes mediated by exosomesαsynuclein,exosomal microRNA can target Parkinson’s diseaserelated genes and participate in oxidative stress,and exosomal DJ-1 protein regulates the level of cellular oxidative stress and affects cytotoxicity.Leucine-rich repetitive kinase 2 of exosomes mediates the formation and accumulation of Lewy bodies and causes neurotoxicity.The above exosomes and their carrying substances can be used as the early stage of Parkinson’s disease biomarkers.(4)At present,there are few related researches on the biomarkers of Parkinson’s disease in exosomes,but the most representative and most widely used is exosomeα-synuclein.Due to the large number and variety of exosomal microRNAs,the expression and role in Parkinson’s disease are not the same,and the research has been hot in the past two years.(5)At present,related research lacks corresponding clinical verification,so it can be used as a future research direction,and the research prospect is broad.Therefore,more potential biomarkers and their mechanisms of action need to be further verified and studied,so as to provide new targets for the early diagnosis and treatment of Parkinson’s disease.(6)The application of exosomes in the clinical diagnosis of Parkinson’s disease still has a lot of research space and development prospects.The application of exosome-mediated cell communication in the diagnosis and treatment of Parkinson’s disease based on clinical trials is the focus and urgent breaking point of future research.