Transportation of key proteins via extracellular vesicles has been recently implicated in various neurodegenerative disorders, including Parkinson’s disease, as a new mechanism of disease spreading and a new source of biomarkers. Extracellular vesicles likely to be derived from the brain can be isolated from peripheral blood and have been reported to contain higher levels of α-synuclein (α-syn) in Parkinson’s disease patients. However, very little is known about extracellular vesicles in multiple system atrophy, a disease that, like Parkinson’s disease, involves pathological α-syn aggregation, though the process is centred around oligodendrocytes in multiple system atrophy. In this study, a novel immunocapture technology was developed to isolate blood CNPase-positive, oligodendrocyte-derived enriched microvesicles (OEMVs), followed by fluorescent nanoparticle tracking analysis and assessment of α-syn levels contained within the OEMVs. The results demonstrated that the concentrations of OEMVs were significantly lower in multiple system atrophy patients, compared to Parkinson’s disease patients and healthy control subjects. It is also noted that the population of OEMVs involved was mainly in the size range closer to that of exosomes, and that the average α-syn concentrations (per vesicle) contained in these OEMVs were not significantly different among the three groups. The phenomenon of reduced OEMVs was again observed in a transgenic mouse model of multiple system atrophy and in primary oligodendrocyte cultures, and the mechanism involved was likely related, at least in part, to an α-syn-mediated interference in the interaction between syntaxin 4 and VAMP2, leading to the dysfunction of the SNARE complex. These results suggest that reduced OEMVs could be an important mechanism related to pathological α-syn aggregation in oligodendrocytes, and the OEMVs found in peripheral blood could be further explored for their potential as multiple system atrophy biomarkers.

中文翻译：

---

多系统萎缩中少突胶质细胞外泌体分泌的减少涉及圈套功能障碍。

近来，关键蛋白通过细胞外小泡的运输与各种神经退行性疾病有关，包括帕金森氏病，是疾病传播的新机制和新的生物标志物来源。可以从外周血中分离出可能源自大脑的细胞外囊泡，据报道在帕金森氏病患者中其细胞中的α-突触核蛋白（α-syn）含量较高。然而，对多系统萎缩中的细胞外囊泡了解甚少，这种疾病与帕金森氏病一样，涉及病理性α-syn聚集，尽管该过程以多系统萎缩中的少突胶质细胞为中心。在这项研究中，开发了一种新型的免疫捕获技术来分离血液中CNPase阳性，少突胶质细胞衍生的富集微泡（OEMV），然后进行荧光纳米颗粒跟踪分析并评估OEMV中所含的α-syn水平。结果表明，与帕金森氏病患者和健康对照组相比，多系统萎缩患者的OEMV浓度显着降低。还应注意，所涉及的OEMV种群的大小范围主要接近外泌体，并且这些OEMV中所含的平均α-syn浓度（每囊泡）在三组之间没有显着差异。在多系统萎缩的转基因小鼠模型和原代少突胶质细胞培养物中再次观察到OEMV减少的现象，并且所涉及的机制可能至少部分与α-syn介导的syntaxin 4之间相互作用的干扰有关。和VAMP2，导致SNARE复合体功能障碍。这些结果表明，降低的OEMVs可能是与少突胶质细胞中病理性α-syn聚集有关的重要机制，并且可以进一步探索在外周血中发现的OEMVs作为多种系统萎缩生物标志物的潜力。