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Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease
Axonal maintenance, plasticity, and regeneration are influenced by signals from neighboring cells, in particular Schwann cells of the peripheral nervous system. Schwann cells produce neurotrophic factors, but the mechanisms by which ciliary neurotrophic factor (CNTF) and other neurotrophic molecules...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483126/ https://www.ncbi.nlm.nih.gov/pubmed/23109669 http://dx.doi.org/10.1083/jcb.201203109 |
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author | Selvaraj, Bhuvaneish Thangaraj Frank, Nicolas Bender, Florian L.P. Asan, Esther Sendtner, Michael |
author_facet | Selvaraj, Bhuvaneish Thangaraj Frank, Nicolas Bender, Florian L.P. Asan, Esther Sendtner, Michael |
author_sort | Selvaraj, Bhuvaneish Thangaraj |
collection | PubMed |
description | Axonal maintenance, plasticity, and regeneration are influenced by signals from neighboring cells, in particular Schwann cells of the peripheral nervous system. Schwann cells produce neurotrophic factors, but the mechanisms by which ciliary neurotrophic factor (CNTF) and other neurotrophic molecules modify the axonal cytoskeleton are not well understood. In this paper, we show that activated signal transducer and activator of transcription-3 (STAT3), an intracellular mediator of the effects of CNTF and other neurotrophic cytokines, acts locally in axons of motoneurons to modify the tubulin cytoskeleton. Specifically, we show that activated STAT3 interacted with stathmin and inhibited its microtubule-destabilizing activity. Thus, ectopic CNTF-mediated activation of STAT3 restored axon elongation and maintenance in motoneurons from progressive motor neuronopathy mutant mice, a mouse model of motoneuron disease. This mechanism could also be relevant for other neurodegenerative diseases and provide a target for new therapies for axonal degeneration. |
format | Online Article Text |
id | pubmed-3483126 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-34831262013-04-29 Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease Selvaraj, Bhuvaneish Thangaraj Frank, Nicolas Bender, Florian L.P. Asan, Esther Sendtner, Michael J Cell Biol Research Articles Axonal maintenance, plasticity, and regeneration are influenced by signals from neighboring cells, in particular Schwann cells of the peripheral nervous system. Schwann cells produce neurotrophic factors, but the mechanisms by which ciliary neurotrophic factor (CNTF) and other neurotrophic molecules modify the axonal cytoskeleton are not well understood. In this paper, we show that activated signal transducer and activator of transcription-3 (STAT3), an intracellular mediator of the effects of CNTF and other neurotrophic cytokines, acts locally in axons of motoneurons to modify the tubulin cytoskeleton. Specifically, we show that activated STAT3 interacted with stathmin and inhibited its microtubule-destabilizing activity. Thus, ectopic CNTF-mediated activation of STAT3 restored axon elongation and maintenance in motoneurons from progressive motor neuronopathy mutant mice, a mouse model of motoneuron disease. This mechanism could also be relevant for other neurodegenerative diseases and provide a target for new therapies for axonal degeneration. The Rockefeller University Press 2012-10-29 /pmc/articles/PMC3483126/ /pubmed/23109669 http://dx.doi.org/10.1083/jcb.201203109 Text en © 2012 Selvaraj et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Selvaraj, Bhuvaneish Thangaraj Frank, Nicolas Bender, Florian L.P. Asan, Esther Sendtner, Michael Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease |
title | Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease |
title_full | Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease |
title_fullStr | Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease |
title_full_unstemmed | Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease |
title_short | Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease |
title_sort | local axonal function of stat3 rescues axon degeneration in the pmn model of motoneuron disease |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483126/ https://www.ncbi.nlm.nih.gov/pubmed/23109669 http://dx.doi.org/10.1083/jcb.201203109 |
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