Nuffield Department of Clinical Neurosciences, University of Oxford Oxford, United Kingdom.
Nuffield Department of Medicine, Target Discovery Institute, University of Oxford Oxford, United Kingdom.
Ann Clin Transl Neurol. 2015 Apr;2(4):353-61. doi: 10.1002/acn3.175. Epub 2015 Feb 6.
Whether circulating microvesicles convey bioactive signals in neurodegenerative diseases remains currently unknown. In this study, we investigated the biochemical composition and biological function of exosomes isolated from sera of patients with Parkinson's disease (PD).
Proteomic analysis was performed on microvesicle preparations from grouped samples of patients with genetic and sporadic forms of PD, amyotrophic lateral sclerosis, and healthy subjects. Nanoparticle-tracking analysis was used to assess the number and size of exosomes between patient groups. To interrogate their biological effect, microvesicles were added to primary rat cortical neurons subjected to either nutrient deprivation or sodium arsenite.
Among 1033 proteins identified, 23 exosome-associated proteins were differentially abundant in PD, including the regulator of exosome biogenesis syntenin 1. These protein changes were detected despite similar exosome numbers across groups suggesting that they may reflect exosome subpopulations with distinct functions. Accordingly, we showed in models of neuronal stress that Parkinson's-derived microvesicles have a protective effect.
Collectively, these data suggest for the first time that immunophenotyping of circulating exosome subpopulations in PD may lead to a better understanding of the systemic response to neurodegeneration and the development of novel therapeutics.
循环微泡是否在神经退行性疾病中传递生物活性信号目前尚不清楚。本研究旨在研究来自帕金森病（PD）患者血清的外泌体的生化组成和生物学功能。
对来自遗传和散发性 PD、肌萎缩侧索硬化症和健康受试者的分组样本的微泡制剂进行蛋白质组学分析。使用纳米颗粒跟踪分析评估患者组之间外泌体的数量和大小。为了研究其生物学效应，将微泡添加到接受营养剥夺或亚砷酸钠处理的原代大鼠皮质神经元中。
在鉴定的 1033 种蛋白质中，23 种外泌体相关蛋白在 PD 中丰度差异，包括外泌体生物发生调节剂 syntenin 1。尽管各组的外泌体数量相似，但仍检测到这些蛋白变化，表明它们可能反映了具有不同功能的外泌体亚群。因此，我们在神经元应激模型中表明，帕金森氏症衍生的微泡具有保护作用。
总的来说，这些数据首次表明，对 PD 中循环外泌体亚群的免疫表型分析可能有助于更好地了解对神经退行性变的全身反应，并开发新的治疗方法。
