The Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3083, Australia.
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC 3052, Australia.
Cells. 2020 Jul 16;9(7):1709. doi: 10.3390/cells9071709.
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by the deposition of misfolded proteins in the motor cortex and motor neurons. Although a multitude of ALS-associated mutated proteins have been identified, several have been linked to small extracellular vesicles such as exosomes involved in cell-cell communication. This study aims to determine the proteome of extracellular vesicles isolated from the motor cortex of ALS subjects and to identify novel ALS-associated deregulated proteins. Motor cortex extracellular vesicles (MCEVs) were isolated from human postmortem ALS (n = 10) and neurological control (NC, n = 5) motor cortex brain tissues and the MCEVs protein content subsequently underwent mass spectrometry analysis, allowing for a panel of ALS-associated proteins to be identified. This panel consists of 16 statistically significant differentially packaged proteins identified in the ALS MCEVs. This includes several upregulated RNA-binding proteins which were determined through pathway analysis to be associated with stress granule dynamics. The identification of these RNA-binding proteins in the ALS MCEVs suggests there may be a relationship between ALS-associated stress granules and ALS MCEV packaging, highlighting a potential role for small extracellular vesicles such as exosomes in the pathogenesis of ALS and as potential peripheral biomarkers for ALS.
肌萎缩侧索硬化症（ALS）是一种神经退行性疾病，其特征是运动皮层和运动神经元中错误折叠的蛋白质沉积。虽然已经鉴定出许多与 ALS 相关的突变蛋白，但有几个与小细胞外囊泡（如参与细胞间通讯的外泌体）有关。本研究旨在确定从 ALS 受试者运动皮层中分离的细胞外囊泡的蛋白质组，并鉴定新的 ALS 相关失调蛋白。从人类死后 ALS（n = 10）和神经学对照（NC，n = 5）运动皮层脑组织中分离运动皮层细胞外囊泡（MCEV），随后对 MCEV 蛋白含量进行质谱分析，鉴定出一组与 ALS 相关的蛋白质。该面板包括在 ALS MCEV 中鉴定出的 16 种统计学上差异包装的蛋白质。其中包括几种上调的 RNA 结合蛋白，通过途径分析确定与应激颗粒动力学有关。在 ALS MCEV 中鉴定出这些 RNA 结合蛋白表明，ALS 相关应激颗粒与 ALS MCEV 包装之间可能存在关系，突出了小细胞外囊泡（如外泌体）在 ALS 发病机制中的潜在作用，以及作为 ALS 的潜在外周生物标志物。
