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Systemic administration of epothilone B promotes axon regeneration and functional recovery after spinal cord injury

After central nervous system (CNS) injury, inhibitory factors in the lesion scar and a poor axon growth potential prevent axon regeneration. Microtubule stabilization reduces scarring and promotes axon growth. However, the cellular mechanisms of this dual effect remain unclear. Here, delayed systemi...

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Bibliographische Detailangaben
Hauptverfasser: Ruschel, Jörg (VerfasserIn) , Sliwinski, Christopher (VerfasserIn) , Blesch, Armin (VerfasserIn) , Weidner, Norbert (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 17 April 2015
In: Science
Year: 2015, Jahrgang: 348, Heft: 6232, Pages: 347-352
ISSN:1095-9203
DOI:10.1126/science.aaa2958
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1126/science.aaa2958
Verlag, Volltext: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445125/
Volltext
Verfasserangaben:Jörg Ruschel, Farida Hellal, Kevin C. Flynn, Sebastian Dupraz, David A. Elliot, Andrea Tedeschi, Margaret Bates, Christopher Sliwinski, Gary Brook, Kristina Dobrint, Michael Peitz, Oliver Brüstle, Michael D. Norenberg, Armin Blesch, Norbert Weidner, Mary Bartlett Bunge, John L. Bixby, and Frank Bradke
Beschreibung
Zusammenfassung:After central nervous system (CNS) injury, inhibitory factors in the lesion scar and a poor axon growth potential prevent axon regeneration. Microtubule stabilization reduces scarring and promotes axon growth. However, the cellular mechanisms of this dual effect remain unclear. Here, delayed systemic administration of a blood-brain barrier permeable microtubule stabilizing drug, epothilone B, decreased scarring after rodent spinal cord injury (SCI) by abrogating polarization and directed migration of scar-forming fibroblasts. Conversely, epothilone B reactivated neuronal polarization by inducing concerted microtubule polymerization into the axon tip, which propelled axon growth through an inhibitory environment. Together, these drug elicited effects promoted axon regeneration and improved motor function after SCI. With recent clinical approval, epothilones hold promise for clinical use after CNS injury.
Beschreibung:Gesehen am 11.07.2017
Beschreibung:Online Resource
ISSN:1095-9203
DOI:10.1126/science.aaa2958

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