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Cells
Volume 9
Issue 7
10.3390/cells9071709
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Article

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

by
Natasha Vassileff
1,
Laura J. Vella
2,3,*,
Harinda Rajapaksha
4,
Mitch Shambrook
1,
Amirmohammad Nasiri Kenari
1,
Catriona McLean
5,6,
Andrew F. Hill
1 and
Lesley Cheng
1,*
1
The Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3083, Australia
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
La Trobe Comprehensive Proteomics Platform, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3083, Australia
5
Victorian Brain Bank, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC 3052, Australia
6
Department of Anatomical Pathology, Alfred Health, Prahran, VIC 3181, Australia
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(7), 1709; https://doi.org/10.3390/cells9071709
Received: 18 May 2020 / Revised: 9 July 2020 / Accepted: 12 July 2020 / Published: 16 July 2020
(This article belongs to the Collection Novel Biomarkers for Alzheimer’s Disease and Other Neurodegenerative Diseases)
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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. View Full-Text
Keywords: Amyotrophic Lateral Sclerosis; ALS; proteomics; exosomes; motor cortex derived extracellular vesicles; extracellular vesicles Amyotrophic Lateral Sclerosis; ALS; proteomics; exosomes; motor cortex derived extracellular vesicles; extracellular vesicles
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MDPI and ACS Style

Vassileff, N.; Vella, L.J.; Rajapaksha, H.; Shambrook, M.; Kenari, A.N.; McLean, C.; Hill, A.F.; Cheng, L. Revealing the Proteome of Motor Cortex Derived Extracellular Vesicles Isolated from Amyotrophic Lateral Sclerosis Human Postmortem Tissues. Cells 2020, 9, 1709. https://doi.org/10.3390/cells9071709

AMA Style

Vassileff N, Vella LJ, Rajapaksha H, Shambrook M, Kenari AN, McLean C, Hill AF, Cheng L. Revealing the Proteome of Motor Cortex Derived Extracellular Vesicles Isolated from Amyotrophic Lateral Sclerosis Human Postmortem Tissues. Cells. 2020; 9(7):1709. https://doi.org/10.3390/cells9071709

Chicago/Turabian Style

Vassileff, Natasha, Laura J. Vella, Harinda Rajapaksha, Mitch Shambrook, Amirmohammad N. Kenari, Catriona McLean, Andrew F. Hill, and Lesley Cheng. 2020. "Revealing the Proteome of Motor Cortex Derived Extracellular Vesicles Isolated from Amyotrophic Lateral Sclerosis Human Postmortem Tissues" Cells 9, no. 7: 1709. https://doi.org/10.3390/cells9071709

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