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

Authors
  • Vassileff, Natasha1
  • Vella, Laura J.2, 3
  • Rajapaksha, Harinda
  • Shambrook, Mitch1
  • Kenari, Amirmohammad Nasiri1
  • McLean, Catriona4
  • Hill, Andrew F.1
  • Cheng, Lesley1
  • 1 (A.F.H.)
  • 2 The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC 3052, Australia
  • 3 Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia
  • 4 Department of Anatomical Pathology, Alfred Health, Prahran, VIC 3181, Australia
Type
Published Article
Journal
Cells
Publisher
MDPI AG
Publication Date
Jul 16, 2020
Volume
9
Issue
7
Identifiers
DOI: 10.3390/cells9071709
PMID: 32708779
PMCID: PMC7407138
Source
PubMed Central
Keywords
License
Green

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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