Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease
Zitieren Sie bitte immer diese 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.…
Autor(en): | Bhuvaneish Thangaraj Selvaraj, Nicolas Frank, Florian L. P. Bender, Esther Asan, Michael Sendtner |
---|---|
URN: | urn:nbn:de:bvb:20-opus-154675 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für Anatomie und Zellbiologie |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | The Journal of Cell Biology |
Erscheinungsjahr: | 2012 |
Band / Jahrgang: | 199 |
Heft / Ausgabe: | 3 |
Erste Seite: | 437 |
Letzte Seite: | 451 |
Originalveröffentlichung / Quelle: | 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 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | Schwann cells; axonal degeneration; ciliary neurotrophic factor (CNTF); transcription-3 (STAT3) |
Datum der Freischaltung: | 08.11.2017 |
EU-Projektnummer / Contract (GA) number: | 259867 |
OpenAIRE: | OpenAIRE |
Lizenz (Deutsch): | CC BY-NC-SA: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Weitergabe unter gleichen Bedingungen |