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RNA-binding protein altered expression and mislocalization in MS
OBJECTIVE: To determine whether there are nuclear depletion and cellular mislocalization of RNA-binding proteins (RBPs) transactivation response DNA-binding protein of 43 kDa (TDP-43), fused in sarcoma (FUS), and polypyrimidine tract–binding protein (PTB) in MS, as is the case in amyotrophic lateral...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176246/ https://www.ncbi.nlm.nih.gov/pubmed/32217641 http://dx.doi.org/10.1212/NXI.0000000000000704 |
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author | Masaki, Katsuhisa Sonobe, Yoshifumi Ghadge, Ghanashyam Pytel, Peter Lépine, Paula Pernin, Florian Cui, Qiao-Ling Antel, Jack P. Zandee, Stephanie Prat, Alexandre Roos, Raymond P. |
author_facet | Masaki, Katsuhisa Sonobe, Yoshifumi Ghadge, Ghanashyam Pytel, Peter Lépine, Paula Pernin, Florian Cui, Qiao-Ling Antel, Jack P. Zandee, Stephanie Prat, Alexandre Roos, Raymond P. |
author_sort | Masaki, Katsuhisa |
collection | PubMed |
description | OBJECTIVE: To determine whether there are nuclear depletion and cellular mislocalization of RNA-binding proteins (RBPs) transactivation response DNA-binding protein of 43 kDa (TDP-43), fused in sarcoma (FUS), and polypyrimidine tract–binding protein (PTB) in MS, as is the case in amyotrophic lateral sclerosis (ALS) and oligodendrocytes infected with Theiler murine encephalomyelitis virus (TMEV), we examined MS lesions and in vitro cultured primary human brain–derived oligodendrocytes. METHODS: Nuclear depletion and mislocalization of TDP-43, FUS, and PTB are thought to contribute to the pathogenesis of ALS and TMEV demyelination. The latter findings prompted us to investigate these RBPs in the demyelinated lesions of MS and in in vitro cultured human brain–derived oligodendrocytes under metabolic stress conditions. RESULTS: We found (1) mislocalized TDP-43 in oligodendrocytes in active lesions in some patients with MS; (2) decreased PTB1 expression in oligodendrocytes in mixed active/inactive demyelinating lesions; (3) decreased nuclear expression of PTB2 in neurons in cortical demyelinating lesions; and (4) nuclear depletion of TDP-43 in oligodendrocytes under metabolic stress induced by low glucose/low nutrient conditions compared with optimal culture conditions. CONCLUSION: TDP-43 has been found to have a key role in oligodendrocyte function and viability, whereas PTB is important in neuronal differentiation, suggesting that altered expression and mislocalization of these RBPs in MS lesions may contribute to the pathogenesis of demyelination and neurodegeneration. Our findings also identify nucleocytoplasmic transport as a target for treatment. |
format | Online Article Text |
id | pubmed-7176246 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-71762462020-05-04 RNA-binding protein altered expression and mislocalization in MS Masaki, Katsuhisa Sonobe, Yoshifumi Ghadge, Ghanashyam Pytel, Peter Lépine, Paula Pernin, Florian Cui, Qiao-Ling Antel, Jack P. Zandee, Stephanie Prat, Alexandre Roos, Raymond P. Neurol Neuroimmunol Neuroinflamm Article OBJECTIVE: To determine whether there are nuclear depletion and cellular mislocalization of RNA-binding proteins (RBPs) transactivation response DNA-binding protein of 43 kDa (TDP-43), fused in sarcoma (FUS), and polypyrimidine tract–binding protein (PTB) in MS, as is the case in amyotrophic lateral sclerosis (ALS) and oligodendrocytes infected with Theiler murine encephalomyelitis virus (TMEV), we examined MS lesions and in vitro cultured primary human brain–derived oligodendrocytes. METHODS: Nuclear depletion and mislocalization of TDP-43, FUS, and PTB are thought to contribute to the pathogenesis of ALS and TMEV demyelination. The latter findings prompted us to investigate these RBPs in the demyelinated lesions of MS and in in vitro cultured human brain–derived oligodendrocytes under metabolic stress conditions. RESULTS: We found (1) mislocalized TDP-43 in oligodendrocytes in active lesions in some patients with MS; (2) decreased PTB1 expression in oligodendrocytes in mixed active/inactive demyelinating lesions; (3) decreased nuclear expression of PTB2 in neurons in cortical demyelinating lesions; and (4) nuclear depletion of TDP-43 in oligodendrocytes under metabolic stress induced by low glucose/low nutrient conditions compared with optimal culture conditions. CONCLUSION: TDP-43 has been found to have a key role in oligodendrocyte function and viability, whereas PTB is important in neuronal differentiation, suggesting that altered expression and mislocalization of these RBPs in MS lesions may contribute to the pathogenesis of demyelination and neurodegeneration. Our findings also identify nucleocytoplasmic transport as a target for treatment. Lippincott Williams & Wilkins 2020-03-26 /pmc/articles/PMC7176246/ /pubmed/32217641 http://dx.doi.org/10.1212/NXI.0000000000000704 Text en Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Article Masaki, Katsuhisa Sonobe, Yoshifumi Ghadge, Ghanashyam Pytel, Peter Lépine, Paula Pernin, Florian Cui, Qiao-Ling Antel, Jack P. Zandee, Stephanie Prat, Alexandre Roos, Raymond P. RNA-binding protein altered expression and mislocalization in MS |
title | RNA-binding protein altered expression and mislocalization in MS |
title_full | RNA-binding protein altered expression and mislocalization in MS |
title_fullStr | RNA-binding protein altered expression and mislocalization in MS |
title_full_unstemmed | RNA-binding protein altered expression and mislocalization in MS |
title_short | RNA-binding protein altered expression and mislocalization in MS |
title_sort | rna-binding protein altered expression and mislocalization in ms |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176246/ https://www.ncbi.nlm.nih.gov/pubmed/32217641 http://dx.doi.org/10.1212/NXI.0000000000000704 |
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