Vassileff, Natasha ORCID: 0000-0001-6554-4496, Vella, Laura J ORCID: 0000-0002-1869-6291, Rajapaksha, Harinda, Shambrook, Mitch, Kenari, Amirmohammad Nasiri, McLean, Catriona ORCID: 0000-0002-0302-5727, Hill, Andrew F ORCID: 0000-0001-5581-2354 and Cheng, Lesley ORCID: 0000-0002-8075-6144 (2020) Revealing the proteome of motor cortex derived extracellular vesicles isolated from amyotrophic lateral sclerosis human postmortem tissues. Cells, 9 (7). ISSN 2073-4409

Abstract

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.

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