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分泌组——细胞外囊泡在神经退行性疾病发病机制和治疗中的作用

Secretome - the role of extracellular vesicles in the pathogenesis and therapy of neurodegenerative diseases.

作者信息

Sulek Anna

机构信息

Lazarski University, Faculty of Medicine, Warsaw, Poland.

出版信息

Postep Psychiatr Neurol. 2024 Sep;33(3):147-162. doi: 10.5114/ppn.2024.144686. Epub 2024 Nov 12.

Abstract

PURPOSE

Extracellular vesicles are the subject of many studies in various medical specialties. Their role in neurodegenerative diseases is increasing and they worth introducing in more detail.

METHODS

This review was performed following an electronic search of the database PubMed/Medline and Web of Science for English-language articles between 2010 and 2024 in the fields of medicine, molecular biology, and biochemistry. Keywords searches included combinations of the following terms: "extracellular vesicles" OR "exosomes" AND "neurodeg*" AND "microRNA" OR "miRNA" AND "AD" OR "PD" OR "ALS" OR "HD". Articles had to be original work or reviews.

RESULTS

The classification of extracellular vesicles is based on their size or origin. Their content is of key importance in communication between cells and can be treated as a physiological determinant of the normal or pathological condition of a body. The cargo transported in the extracellular space and over longer distances in various body fluids is diversified and may be nucleic acids (DNA, RNA, miRNA) as well as proteins and lipids, and, in the case of apoptotic bodies also a cell's organelles. Exosomes are the most thoroughly studied extracellular vesicles and the most often considered for therapeutic applications. Vesicles carrying biological substances in the body perform three basic functions: participation in a pathological mechanism, a biomarker role that also has diagnostic and prognostic functions, and a role in therapeutic activities. In the case of neurodegenerative diseases, it appears that extracellular vesicles can transport misfolded proteins, initiating pathological processes in previously normal cells.

CONCLUSIONS

The transport of various substances enclosed in vesicles seems to be very promising in therapeutic prospects in various diseases, and the possibility of their crossing the blood-brain barrier particularly indicates diseases of the central nervous system. Despite many years of research on extracellular vesicles in the context of neurodegenerative diseases, their practical use is currently limited to studies on animal and cellular models, and their practical application in clinical trials in neurodegenerative diseases is to date extremely rare.

摘要

目的

细胞外囊泡是各个医学专业众多研究的主题。它们在神经退行性疾病中的作用日益受到关注,值得更详细地介绍。

方法

本综述通过对数据库PubMed/Medline和Web of Science进行电子检索,查找2010年至2024年期间医学、分子生物学和生物化学领域的英文文章。关键词搜索包括以下术语的组合:“细胞外囊泡”或“外泌体”以及“神经*”和“微小RNA”或“miRNA”以及“阿尔茨海默病”或“帕金森病”或“肌萎缩侧索硬化症”或“亨廷顿舞蹈症”。文章必须是原创作品或综述。

结果

细胞外囊泡的分类基于其大小或来源。它们的内容物在细胞间通讯中至关重要,可被视为身体正常或病理状态的生理决定因素。在细胞外空间以及在各种体液中远距离运输的货物多种多样,可能是核酸(DNA、RNA、miRNA)以及蛋白质和脂质,而对于凋亡小体,还包括细胞的细胞器。外泌体是研究最深入的细胞外囊泡,也是最常被考虑用于治疗应用的囊泡。在体内携带生物物质的囊泡具有三种基本功能:参与病理机制、具有诊断和预后功能的生物标志物作用以及在治疗活动中的作用。在神经退行性疾病中,细胞外囊泡似乎可以运输错误折叠的蛋白质,从而在先前正常的细胞中引发病理过程。

结论

囊泡中包裹的各种物质的运输在各种疾病的治疗前景中似乎非常有前景,它们穿过血脑屏障的可能性尤其适用于中枢神经系统疾病。尽管在神经退行性疾病背景下对细胞外囊泡进行了多年研究,但其实际应用目前仅限于动物和细胞模型研究,迄今为止,它们在神经退行性疾病临床试验中的实际应用极为罕见。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180b/11635433/cbe32bf90e1a/PPN-33-55069-g001.jpg

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