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Dock3 protects myelin in the cuprizone model for demyelination
Dedicator of cytokinesis 3 (Dock3) belongs to an atypical family of the guanine nucleotide exchange factors. It is predominantly expressed in the neural tissues and causes cellular morphological changes by activating the small GTPase Rac1. We previously reported that Dock3 overexpression protects re...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454328/ https://www.ncbi.nlm.nih.gov/pubmed/25165881 http://dx.doi.org/10.1038/cddis.2014.357 |
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author | Namekata, K Kimura, A Harada, C Yoshida, H Matsumoto, Y Harada, T |
author_facet | Namekata, K Kimura, A Harada, C Yoshida, H Matsumoto, Y Harada, T |
author_sort | Namekata, K |
collection | PubMed |
description | Dedicator of cytokinesis 3 (Dock3) belongs to an atypical family of the guanine nucleotide exchange factors. It is predominantly expressed in the neural tissues and causes cellular morphological changes by activating the small GTPase Rac1. We previously reported that Dock3 overexpression protects retinal ganglion cells from excitotoxic cell death. Oligodendrocytes are the myelinating cells of axons in the central nervous system and these cells are damaged in demyelinating disorders including multiple sclerosis (MS) and optic neuritis. In this study, we examined if Dock3 is expressed in oligodendrocytes and if increasing Dock3 signals can suppress demyelination in a cuprizone-induced demyelination model, an animal model of MS. We demonstrate that Dock3 is expressed in oligodendrocytes and Dock3 overexpression protects myelin in the corpus callosum following cuprizone treatment. Furthermore, we show that cuprizone demyelinates optic nerves and the extent of demyelination is ameliorated in mice overexpressing Dock3. Cuprizone treatment impairs visual function, which was demonstrated by multifocal electroretinograms, an established non-invasive method, and Dock3 overexpression prevented this effect. In mice overexpressing Dock3, Erk activation is increased, suggesting this may at least partly explain the observed protective effects. Our findings suggest that Dock3 may be a therapeutic target for demyelinating disorders including optic neuritis. |
format | Online Article Text |
id | pubmed-4454328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44543282015-06-15 Dock3 protects myelin in the cuprizone model for demyelination Namekata, K Kimura, A Harada, C Yoshida, H Matsumoto, Y Harada, T Cell Death Dis Original Article Dedicator of cytokinesis 3 (Dock3) belongs to an atypical family of the guanine nucleotide exchange factors. It is predominantly expressed in the neural tissues and causes cellular morphological changes by activating the small GTPase Rac1. We previously reported that Dock3 overexpression protects retinal ganglion cells from excitotoxic cell death. Oligodendrocytes are the myelinating cells of axons in the central nervous system and these cells are damaged in demyelinating disorders including multiple sclerosis (MS) and optic neuritis. In this study, we examined if Dock3 is expressed in oligodendrocytes and if increasing Dock3 signals can suppress demyelination in a cuprizone-induced demyelination model, an animal model of MS. We demonstrate that Dock3 is expressed in oligodendrocytes and Dock3 overexpression protects myelin in the corpus callosum following cuprizone treatment. Furthermore, we show that cuprizone demyelinates optic nerves and the extent of demyelination is ameliorated in mice overexpressing Dock3. Cuprizone treatment impairs visual function, which was demonstrated by multifocal electroretinograms, an established non-invasive method, and Dock3 overexpression prevented this effect. In mice overexpressing Dock3, Erk activation is increased, suggesting this may at least partly explain the observed protective effects. Our findings suggest that Dock3 may be a therapeutic target for demyelinating disorders including optic neuritis. Nature Publishing Group 2014-08 2014-08-28 /pmc/articles/PMC4454328/ /pubmed/25165881 http://dx.doi.org/10.1038/cddis.2014.357 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/3.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Original Article Namekata, K Kimura, A Harada, C Yoshida, H Matsumoto, Y Harada, T Dock3 protects myelin in the cuprizone model for demyelination |
title | Dock3 protects myelin in the cuprizone model for demyelination |
title_full | Dock3 protects myelin in the cuprizone model for demyelination |
title_fullStr | Dock3 protects myelin in the cuprizone model for demyelination |
title_full_unstemmed | Dock3 protects myelin in the cuprizone model for demyelination |
title_short | Dock3 protects myelin in the cuprizone model for demyelination |
title_sort | dock3 protects myelin in the cuprizone model for demyelination |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454328/ https://www.ncbi.nlm.nih.gov/pubmed/25165881 http://dx.doi.org/10.1038/cddis.2014.357 |
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