Pathological Proteins Are Transported by Extracellular Vesicles of Sporadic Amyotrophic Lateral Sclerosis Patients
Amyotrophic lateral sclerosis (ALS) is a progressive adult-onset neurodegenerative disease, that affects cortical, bulbar and spinal motor neurons, and it is considered a proteinopathy, in which pathological proteins (SOD1, TDP-43, and FUS) may accumulate and interfere with neuronal functions eventu...
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doaj-379cbefa84374363b4d69f114851a77b2020-11-24T21:18:01ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-07-011210.3389/fnins.2018.00487375309Pathological Proteins Are Transported by Extracellular Vesicles of Sporadic Amyotrophic Lateral Sclerosis PatientsDaisy Sproviero0Sabrina La Salvia1Marta Giannini2Marta Giannini3Valeria Crippa4Stella Gagliardi5Stefano Bernuzzi6Luca Diamanti7Luca Diamanti8Mauro Ceroni9Mauro Ceroni10Orietta Pansarasa11Angelo Poletti12Cristina Cereda13Genomic and Post-Genomic Center, IRCCS Mondino Foundation, Pavia, ItalyGenomic and Post-Genomic Center, IRCCS Mondino Foundation, Pavia, ItalyGenomic and Post-Genomic Center, IRCCS Mondino Foundation, Pavia, ItalyDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, ItalyDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, Milan, ItalyGenomic and Post-Genomic Center, IRCCS Mondino Foundation, Pavia, ItalyImmunohematological and Transfusional Service and Centre of Transplantation Immunology, IRCCS Foundation San Matteo, Pavia, ItalyDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, ItalyDivision of General Neurology, IRCCS Mondino Foundation, Pavia, ItalyDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, ItalyDivision of General Neurology, IRCCS Mondino Foundation, Pavia, ItalyGenomic and Post-Genomic Center, IRCCS Mondino Foundation, Pavia, ItalyDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, Milan, ItalyGenomic and Post-Genomic Center, IRCCS Mondino Foundation, Pavia, ItalyAmyotrophic lateral sclerosis (ALS) is a progressive adult-onset neurodegenerative disease, that affects cortical, bulbar and spinal motor neurons, and it is considered a proteinopathy, in which pathological proteins (SOD1, TDP-43, and FUS) may accumulate and interfere with neuronal functions eventually leading to cell death. These proteins can be released from cells and transported in the body fluids by extracellular vesicles (EVs). EVs are spherical vesicles, which are classified mainly in microvesicles (MVs) and exosomes (EXOs) based on their biogenesis, size and surface markers. In this study we characterized MVs and EXOs isolated from plasma of sporadic ALS patients and healthy controls and determined their number, size and SOD1, TDP-43, and FUS protein composition. No variation was found in the number of EVs between ALS patients and controls. However, the mean size both for MVs and for EXOs resulted increased in ALS patients compared to controls. MVs derived from ALS patients were enriched in SOD1, TDP-43, phospho-TDP-43, and FUS proteins compared to CTRLs. SOD1 was generally more concentrated in EXOs than in MVs, while TDP-43 and FUS protein levels were slightly higher in MVs than in EXOs. We demonstrated that MVs and EXOs size were increased in ALS patients compared to controls and that MVs of ALS patients were enriched with toxic proteins compared to CTRLs. EXOs did not show any protein changes. These data may suggest that MVs can transport toxic proteins and might play a role in prion-like propagation of ALS disease.https://www.frontiersin.org/article/10.3389/fnins.2018.00487/fullamyotrophic lateral sclerosisproteinopathyextracellular vesiclesmicrovesiclesexosomesSOD-1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Daisy Sproviero Sabrina La Salvia Marta Giannini Marta Giannini Valeria Crippa Stella Gagliardi Stefano Bernuzzi Luca Diamanti Luca Diamanti Mauro Ceroni Mauro Ceroni Orietta Pansarasa Angelo Poletti Cristina Cereda |
spellingShingle |
Daisy Sproviero Sabrina La Salvia Marta Giannini Marta Giannini Valeria Crippa Stella Gagliardi Stefano Bernuzzi Luca Diamanti Luca Diamanti Mauro Ceroni Mauro Ceroni Orietta Pansarasa Angelo Poletti Cristina Cereda Pathological Proteins Are Transported by Extracellular Vesicles of Sporadic Amyotrophic Lateral Sclerosis Patients Frontiers in Neuroscience amyotrophic lateral sclerosis proteinopathy extracellular vesicles microvesicles exosomes SOD-1 |
author_facet |
Daisy Sproviero Sabrina La Salvia Marta Giannini Marta Giannini Valeria Crippa Stella Gagliardi Stefano Bernuzzi Luca Diamanti Luca Diamanti Mauro Ceroni Mauro Ceroni Orietta Pansarasa Angelo Poletti Cristina Cereda |
author_sort |
Daisy Sproviero |
title |
Pathological Proteins Are Transported by Extracellular Vesicles of Sporadic Amyotrophic Lateral Sclerosis Patients |
title_short |
Pathological Proteins Are Transported by Extracellular Vesicles of Sporadic Amyotrophic Lateral Sclerosis Patients |
title_full |
Pathological Proteins Are Transported by Extracellular Vesicles of Sporadic Amyotrophic Lateral Sclerosis Patients |
title_fullStr |
Pathological Proteins Are Transported by Extracellular Vesicles of Sporadic Amyotrophic Lateral Sclerosis Patients |
title_full_unstemmed |
Pathological Proteins Are Transported by Extracellular Vesicles of Sporadic Amyotrophic Lateral Sclerosis Patients |
title_sort |
pathological proteins are transported by extracellular vesicles of sporadic amyotrophic lateral sclerosis patients |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2018-07-01 |
description |
Amyotrophic lateral sclerosis (ALS) is a progressive adult-onset neurodegenerative disease, that affects cortical, bulbar and spinal motor neurons, and it is considered a proteinopathy, in which pathological proteins (SOD1, TDP-43, and FUS) may accumulate and interfere with neuronal functions eventually leading to cell death. These proteins can be released from cells and transported in the body fluids by extracellular vesicles (EVs). EVs are spherical vesicles, which are classified mainly in microvesicles (MVs) and exosomes (EXOs) based on their biogenesis, size and surface markers. In this study we characterized MVs and EXOs isolated from plasma of sporadic ALS patients and healthy controls and determined their number, size and SOD1, TDP-43, and FUS protein composition. No variation was found in the number of EVs between ALS patients and controls. However, the mean size both for MVs and for EXOs resulted increased in ALS patients compared to controls. MVs derived from ALS patients were enriched in SOD1, TDP-43, phospho-TDP-43, and FUS proteins compared to CTRLs. SOD1 was generally more concentrated in EXOs than in MVs, while TDP-43 and FUS protein levels were slightly higher in MVs than in EXOs. We demonstrated that MVs and EXOs size were increased in ALS patients compared to controls and that MVs of ALS patients were enriched with toxic proteins compared to CTRLs. EXOs did not show any protein changes. These data may suggest that MVs can transport toxic proteins and might play a role in prion-like propagation of ALS disease. |
topic |
amyotrophic lateral sclerosis proteinopathy extracellular vesicles microvesicles exosomes SOD-1 |
url |
https://www.frontiersin.org/article/10.3389/fnins.2018.00487/full |
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