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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...

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Autores principales: Selvaraj, Bhuvaneish Thangaraj, Frank, Nicolas, Bender, Florian L.P., Asan, Esther, Sendtner, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
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.
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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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