School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551, Singapore.
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551, Singapore; Department of Health Sciences, Faculty of Applied Health Sciences, Brock University, St Catharines, Ontario L2S 3A1, Canada.
Exp Neurol. 2022 Sep;355:114149. doi: 10.1016/j.expneurol.2022.114149. Epub 2022 Jun 19.
Extracellular vesicles (EVs) are small lipid bilayer particles ubiquitously released by almost every cell type. A specific and selective constituents of EVs loaded with variety of proteins, lipids, small noncoding RNAs, and long non-coding RNAs are reflective of cellular events, type, and physiologic/pathophysiologic status of the cell of origin. Moreover, these molecular contents carry information from the cell of origin to recipient cells, modulating intercellular communication. Recent studies demonstrated that EVs not only play a neuroprotective role by mediating the removal of toxic proteins, but also emerge as an important player in various neurodegenerative disease onset and progression through facilitating of misfolded proteins propagation. For this reason, neurodegenerative disease-associated differences in EV proteome relative to normal EVs can be used to fulfil diagnostic, prognostic, and therapeutic purposes. Nonetheless, characterizing EV proteome obtained from biological samples (brain tissue and body fluids, including urea, blood, saliva, and CSF) is a challenging task. Herein, we review the status of EV proteome profiling and the updated discovery of potential biomarkers for the diagnosis of neurodegenerative disease with an emphasis on the integration of high-throughput advanced mass spectrometry (MS) technologies for both qualitative and quantitative analysis of EVs in different clinical tissue/body fluid samples in past five years.
细胞外囊泡（EVs）是几乎所有细胞类型普遍释放的小脂质双层颗粒。EVs 中装载着各种蛋白质、脂质、小非编码 RNA 和长非编码 RNA，它们是细胞来源的细胞类型、生理/病理状态的特异性和选择性组成部分。此外，这些分子内容物携带来自细胞来源的信息到受体细胞，调节细胞间通讯。最近的研究表明，EVs 不仅通过介导毒性蛋白的清除发挥神经保护作用，而且通过促进错误折叠蛋白的传播，也成为各种神经退行性疾病发病和进展的重要参与者。因此，与正常 EVs 相比，神经退行性疾病相关的 EV 蛋白质组学差异可用于满足诊断、预后和治疗目的。尽管如此，从生物样本（脑组织和体液，包括尿素、血液、唾液和 CSF）中获得 EV 蛋白质组学的特征仍然是一项具有挑战性的任务。在此，我们综述了 EV 蛋白质组学分析的现状以及最新发现的用于诊断神经退行性疾病的潜在生物标志物，重点介绍了过去五年中用于不同临床组织/体液样本中 EV 的定性和定量分析的高通量先进质谱（MS）技术的整合。
