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

• DOI: 10.3390/cells9071709
• Publication Date: 2020-07-21T10:38:55Z
• Authors: Natasha Vassileff; Laura J. Vella; Harinda Rajapaksha; Mitch Shambrook; Amirmohammad Nasi...; Catriona McLean; Andrew F. Hill; Lesley Cheng
• Keywords: 0301 basic medicine; amyotrophic lateral sclerosis; 570; Proteome; 610; exosomes; motor cortex derived extracellular vesicles; Exosomes; Models, Biological; Article; Extracellular Vesicles; 03 medical and health sciences; proteomics; 3205 Medical biochemistry and metabolomics; Humans; Protein Interaction Maps; Uncategorized; QH573-671; Amyotrophic Lateral Sclerosis; Motor Cortex; biomarkers; Chancellery; Gene Ontology; Case-Control Studies; Postmortem Changes; 3209 Neurosciences; exomes; ALS; extracellular vesicles; Cytology; Lysosomes

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.