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Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease

Please always quote using this URN: urn:nbn:de:bvb:20-opus-154675
  • 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 locallyAxonal 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.show moreshow less

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Metadaten
Author: Bhuvaneish Thangaraj Selvaraj, Nicolas Frank, Florian L. P. Bender, Esther Asan, Michael Sendtner
URN:urn:nbn:de:bvb:20-opus-154675
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Anatomie und Zellbiologie
Language:English
Parent Title (English):The Journal of Cell Biology
Year of Completion:2012
Volume:199
Issue:3
Source:The Journal of Cell Biology Vol. 199, No. 3, 437-451 (2012). DOI: 10.1083/jcb.201203109
DOI:https://doi.org/10.1083/jcb.201203109
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Schwann cells; axonal degeneration; ciliary neurotrophic factor (CNTF); transcription-3 (STAT3)
Release Date:2017/11/08
First Page:437
Last Page:451
EU-Project number / Contract (GA) number:259867
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY-NC-SA: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Weitergabe unter gleichen Bedingungen