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Extracellular vesicles and amyotrophic lateral sclerosis: from misfolded protein vehicles to promising clinical biomarkers.
Cellular and Molecular Life Sciences ( IF 8 ) Pub Date : 2020-08-16 , DOI: 10.1007/s00018-020-03619-3
Delia Gagliardi 1 , Nereo Bresolin 1, 2 , Giacomo Pietro Comi 1, 2 , Stefania Corti 1, 2
Affiliation  

Extracellular vesicles (EVs) are small reservoirs of different molecules and important mediators of cell-to-cell communication. As putative vehicles of misfolded protein propagation between cells, they have drawn substantial attention in the field of amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Moreover, exosome-mediated non-coding RNA delivery may play a crucial role in ALS, given the relevance of RNA homeostasis in disease pathogenesis. Since EVs can enter the systemic circulation and are easily detectable in patients’ biological fluids, they have generated broad interest both as diagnostic and prognostic biomarkers and as valuable tools in understanding disease pathogenesis. Here, after a brief introduction on biogenesis and functions of EVs, we aim to investigate their role in neurodegenerative disorders, especially ALS. Specifically, we focus on the main findings supporting EV-mediated protein and RNA transmission in ALS in vitro and in vivo models. Then, we provide an overview of clinical applications of EVs, summarizing the most relevant studies able to detect EVs in blood and cerebrospinal fluid (CSF) of ALS patients, underlying their potential use in aiding diagnosis and prognosis. Finally, we explore the therapeutic applications of EVs in ALS, either as targets or as vehicles of proteins, nucleic acids and molecular drugs.



中文翻译:

细胞外囊泡和肌萎缩性侧索硬化:从错误折叠的蛋白载体到有希望的临床生物标志物。

细胞外囊泡(EVs)是不同分子的小型储存库,是细胞间通讯的重要介质。作为错误折叠的蛋白在细胞之间传播的假定载体,它们在肌萎缩性侧索硬化症(ALS)和其他神经退行性疾病领域引起了广泛关注。此外,考虑到RNA稳态与疾病发病机制的相关性,外来体介导的非编码RNA传递可能在ALS中起关键作用。由于电动汽车可以进入全身循环并且很容易在患者的生物体液中检测到,因此,电动汽车作为诊断和预后生物标志物以及了解疾病发病机理的重要工具都引起了广泛关注。在这里,在简要介绍EV的生物发生和功能后,我们旨在研究其在神经退行性疾病中的作用,特别是ALS。具体来说,我们重点关注支持EV介导的蛋白和RNA在ALS体内和体外模型中传播的主要发现。然后,我们概述了电动汽车的临床应用,总结了能够检测ALS患者血液和脑脊液(CSF)中的电动汽车的最相关研究,这些电动汽车在帮助诊断和预后方面具有潜在的用途。最后,我们探索了EV在ALS中的治疗应用,无论是作为靶标还是作为蛋白质,核酸和分子药物的载体。潜在地帮助诊断和预后。最后,我们探索了EV在ALS中的治疗应用,无论是作为靶标还是作为蛋白质,核酸和分子药物的载体。潜在地帮助诊断和预后。最后,我们探索了EV在ALS中的治疗应用,无论是作为靶标还是作为蛋白质,核酸和分子药物的载体。

更新日期:2020-08-16
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