Quiroz-Baez Ricardo, Hernández-Ortega Karina, Martínez-Martínez Eduardo
Departamento de Investigación Básica, Dirección de Investigación, Instituto Nacional de Geriatría, Ciudad de México, Mexico.
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mexico.
Front Neurol. 2020 Dec 11;11:580030. doi: 10.3389/fneur.2020.580030. eCollection 2020.
Extracellular vesicles (EVs) are involved in the development and progression of neurodegenerative diseases, including Alzheimer's and Parkinson's disease. Moreover, EVs have the capacity to modify the physiology of neuronal circuits by transferring proteins, RNA, lipids, and metabolites. The proteomic characterization of EVs (exosomes and microvesicles) from preclinical models and patient samples has the potential to reveal new proteins and molecular networks that affect the normal physiology prior to the appearance of traditional biomarkers of neurodegeneration. Noteworthy, many of the genetic risks associated to the development of Alzheimer's and Parkinson's disease affect the crosstalk between mitochondria, endosomes, and lysosomes. Recent research has focused on determining the role of endolysosomal trafficking in the onset of neurodegenerative diseases. Proteomic studies indicate an alteration of biogenesis and molecular content of EVs as a result of endolysosomal and autophagic dysfunction. In this review, we discuss the status of EV proteomic characterization and their usefulness in discovering new biomarkers for the differential diagnosis of neurodegenerative diseases. Despite the challenges related to the failure to follow a standard isolation protocol and their implementation for a clinical setting, the analysis of EV proteomes has revealed the presence of key proteins with post-translational modifications that can be measured in peripheral fluids.
细胞外囊泡（EVs）参与神经退行性疾病的发生和发展，包括阿尔茨海默病和帕金森病。此外，EVs能够通过转运蛋白质、RNA、脂质和代谢物来改变神经回路的生理功能。对临床前模型和患者样本中的EVs（外泌体和微囊泡）进行蛋白质组学表征，有可能揭示在神经退行性变的传统生物标志物出现之前影响正常生理功能的新蛋白质和分子网络。值得注意的是，许多与阿尔茨海默病和帕金森病发生相关的遗传风险影响线粒体、内体和溶酶体之间的相互作用。最近的研究集中在确定内溶酶体运输在神经退行性疾病发病中的作用。蛋白质组学研究表明，内溶酶体和自噬功能障碍会导致EVs的生物发生和分子含量发生改变。在这篇综述中，我们讨论了EVs蛋白质组学表征的现状及其在发现用于神经退行性疾病鉴别诊断的新生物标志物方面的作用。尽管在遵循标准分离方案及其在临床环境中的应用方面存在挑战，但对EVs蛋白质组的分析已经揭示了存在可在外周血中检测到的具有翻译后修饰的关键蛋白质。
