Revealing the Proteome of Motor Cortex Derived Extracellular Vesicles Isolated from Amyotrophic Lateral Sclerosis Human Postmortem Tissues

• Published in: Cells (Basel, Switzerland) Vol. 9; no. 7; p. 1709
• Main Authors: Vassileff, Natasha, Vella, Laura J., Rajapaksha, Harinda, Shambrook, Mitch, Kenari, Amirmohammad Nasiri, McLean, Catriona, Hill, Andrew F., Cheng, Lesley
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.07.2020; MDPI
• Subjects: ALS; Amyotrophic Lateral Sclerosis; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - pathology; Biomarkers; Case-Control Studies; Cell interactions; Cortex (motor); Exosomes; Exosomes - metabolism; Extracellular vesicles; Extracellular Vesicles - metabolism; Extracellular Vesicles - ultrastructure; Gene Ontology; Humans; Lysosomes - metabolism; Mass spectroscopy; Models, Biological; Motor Cortex - metabolism; motor cortex derived extracellular vesicles; Motor neurons; Motor task performance; Mutation; Nanoparticles; Neurodegenerative diseases; Pathogenesis; Postmortem Changes; Protein folding; Protein Interaction Maps; Proteins; Proteome - metabolism; Proteomes; proteomics; Ribonucleic acid; RNA; RNA-binding protein; Statistical analysis; Sucrose; Transmission electron microscopy; St Louis Missouri; United Kingdom > UK; United States > US; ALS; Amyotrophic Lateral Sclerosis; extracellular vesicles; proteomics; exosomes; motor cortex derived extracellular vesicles
• ISSN: 2073-4409; 2073-4409
• 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.