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Survival Motor Neuron Protein is Released from Cells in Exosomes: A Potential Biomarker for Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is caused by homozygous mutation of the survival motor neuron 1 (SMN1) gene. Disease severity inversely correlates to the amount of SMN protein produced from the homologous SMN2 gene. We show that SMN protein is naturally released in exosomes from all cell types examine...

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Autores principales: Nash, Leslie A., McFall, Emily R., Perozzo, Amanda M., Turner, Maddison, Poulin, Kathy L., De Repentigny, Yves, Burns, Joseph K., McMillan, Hugh J., Warman Chardon, Jodi, Burger, Dylan, Kothary, Rashmi, Parks, Robin J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655039/
https://www.ncbi.nlm.nih.gov/pubmed/29066780
http://dx.doi.org/10.1038/s41598-017-14313-z
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author Nash, Leslie A.
McFall, Emily R.
Perozzo, Amanda M.
Turner, Maddison
Poulin, Kathy L.
De Repentigny, Yves
Burns, Joseph K.
McMillan, Hugh J.
Warman Chardon, Jodi
Burger, Dylan
Kothary, Rashmi
Parks, Robin J.
author_facet Nash, Leslie A.
McFall, Emily R.
Perozzo, Amanda M.
Turner, Maddison
Poulin, Kathy L.
De Repentigny, Yves
Burns, Joseph K.
McMillan, Hugh J.
Warman Chardon, Jodi
Burger, Dylan
Kothary, Rashmi
Parks, Robin J.
author_sort Nash, Leslie A.
collection PubMed
description Spinal muscular atrophy (SMA) is caused by homozygous mutation of the survival motor neuron 1 (SMN1) gene. Disease severity inversely correlates to the amount of SMN protein produced from the homologous SMN2 gene. We show that SMN protein is naturally released in exosomes from all cell types examined. Fibroblasts from patients or a mouse model of SMA released exosomes containing reduced levels of SMN protein relative to normal controls. Cells overexpressing SMN protein released exosomes with dramatically elevated levels of SMN protein. We observed enhanced quantities of exosomes in the medium from SMN-depleted cells, and in serum from a mouse model of SMA and a patient with Type 3 SMA, suggesting that SMN-depletion causes a deregulation of exosome release or uptake. The quantity of SMN protein contained in the serum-derived exosomes correlated with the genotype of the animal, with progressively less protein in carrier and affected animals compared to wildtype mice. SMN protein was easily detectable in exosomes isolated from human serum, with a reduction in the amount of SMN protein in exosomes from a patient with Type 3 SMA compared to a normal control. Our results suggest that exosome-derived SMN protein may serve as an effective biomarker for SMA.
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spelling pubmed-56550392017-10-31 Survival Motor Neuron Protein is Released from Cells in Exosomes: A Potential Biomarker for Spinal Muscular Atrophy Nash, Leslie A. McFall, Emily R. Perozzo, Amanda M. Turner, Maddison Poulin, Kathy L. De Repentigny, Yves Burns, Joseph K. McMillan, Hugh J. Warman Chardon, Jodi Burger, Dylan Kothary, Rashmi Parks, Robin J. Sci Rep Article Spinal muscular atrophy (SMA) is caused by homozygous mutation of the survival motor neuron 1 (SMN1) gene. Disease severity inversely correlates to the amount of SMN protein produced from the homologous SMN2 gene. We show that SMN protein is naturally released in exosomes from all cell types examined. Fibroblasts from patients or a mouse model of SMA released exosomes containing reduced levels of SMN protein relative to normal controls. Cells overexpressing SMN protein released exosomes with dramatically elevated levels of SMN protein. We observed enhanced quantities of exosomes in the medium from SMN-depleted cells, and in serum from a mouse model of SMA and a patient with Type 3 SMA, suggesting that SMN-depletion causes a deregulation of exosome release or uptake. The quantity of SMN protein contained in the serum-derived exosomes correlated with the genotype of the animal, with progressively less protein in carrier and affected animals compared to wildtype mice. SMN protein was easily detectable in exosomes isolated from human serum, with a reduction in the amount of SMN protein in exosomes from a patient with Type 3 SMA compared to a normal control. Our results suggest that exosome-derived SMN protein may serve as an effective biomarker for SMA. Nature Publishing Group UK 2017-10-24 /pmc/articles/PMC5655039/ /pubmed/29066780 http://dx.doi.org/10.1038/s41598-017-14313-z Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Nash, Leslie A.
McFall, Emily R.
Perozzo, Amanda M.
Turner, Maddison
Poulin, Kathy L.
De Repentigny, Yves
Burns, Joseph K.
McMillan, Hugh J.
Warman Chardon, Jodi
Burger, Dylan
Kothary, Rashmi
Parks, Robin J.
Survival Motor Neuron Protein is Released from Cells in Exosomes: A Potential Biomarker for Spinal Muscular Atrophy
title Survival Motor Neuron Protein is Released from Cells in Exosomes: A Potential Biomarker for Spinal Muscular Atrophy
title_full Survival Motor Neuron Protein is Released from Cells in Exosomes: A Potential Biomarker for Spinal Muscular Atrophy
title_fullStr Survival Motor Neuron Protein is Released from Cells in Exosomes: A Potential Biomarker for Spinal Muscular Atrophy
title_full_unstemmed Survival Motor Neuron Protein is Released from Cells in Exosomes: A Potential Biomarker for Spinal Muscular Atrophy
title_short Survival Motor Neuron Protein is Released from Cells in Exosomes: A Potential Biomarker for Spinal Muscular Atrophy
title_sort survival motor neuron protein is released from cells in exosomes: a potential biomarker for spinal muscular atrophy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655039/
https://www.ncbi.nlm.nih.gov/pubmed/29066780
http://dx.doi.org/10.1038/s41598-017-14313-z
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