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Revealing the Proteome of Motor Cortex Derived Extracellular Vesicles Isolated from Amyotrophic Lateral Sclerosis Human Postmortem Tissues
journal contributionposted on 14.01.2021, 05:53 by Natasha VassileffNatasha Vassileff, LJ Vella, Kolin RajapakshaKolin Rajapaksha, Mitch ShambrookMitch Shambrook, Amirmohammad Nasiri KenariAmirmohammad Nasiri Kenari, C McLean, Andrew HillAndrew Hill, Lesley SimLesley Sim
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.
Motor Neuron Disease Foundation Australia and the National Health and Medical Research Council.
Pagination20p. (p. 1-20)
PublisherMultidisciplinary Digital Publishing Institute (MDPI)
Rights StatementThe Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.
Science & TechnologyLife Sciences & BiomedicineCell BiologyAmyotrophic Lateral SclerosisALSproteomicsexosomesmotor cortex derived extracellular vesiclesextracellular vesiclesFRONTOTEMPORAL LOBAR DEGENERATIONSTRESS GRANULESSUPEROXIDE-DISMUTASEINTERACTING PROTEINSMULTIVESICULAR BODIESATTENUATES DISEASEBINDING PROTEINMOUSE MODELAUTOPHAGYTDP-43