Journal Article

DZNE-2020-04215

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Systemic administration of epothilone B promotes axon regeneration after spinal cord injury.

Ruschel, J. (First author)DZNE* ; Hellal, F.DZNE* ; Flynn, K. C.DZNE* ; Dupraz, S.DZNE* ; Elliott, D. A.DZNE* ; Tedeschi, A.DZNE* ; Bates, M. ; Sliwinski, C. ; Brook, G. ; Dobrindt, K. ; Peitz, M. ; Brüstle, O. ; Norenberg, M. D. ; Blesch, A. ; Weidner, N. ; Bunge, M. B. ; Bixby, J. L. ; Bradke, F. (Last author)DZNE*

2015
Assoc.60841 Washington, DC

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Please use a persistent id in citations: doi:10.1126/science.aaa2958

Abstract: After central nervous system (CNS) injury, inhibitory factors in the lesion scar and 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 (epoB), 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.

Keyword(s): Animals (MeSH) ; Axons: drug effects (MeSH) ; Axons: physiology (MeSH) ; Cell Movement: drug effects (MeSH) ; Cell Polarity: drug effects (MeSH) ; Cicatrix: pathology (MeSH) ; Cicatrix: prevention & control (MeSH) ; Epothilones: administration & dosage (MeSH) ; Fibroblasts: drug effects (MeSH) ; Fibroblasts: pathology (MeSH) ; Humans (MeSH) ; Meninges: drug effects (MeSH) ; Meninges: pathology (MeSH) ; Motor Activity: drug effects (MeSH) ; Nerve Regeneration: drug effects (MeSH) ; Neurons: drug effects (MeSH) ; Neurons: pathology (MeSH) ; Rats (MeSH) ; Spinal Cord Injuries: drug therapy (MeSH) ; Spinal Cord Injuries: pathology (MeSH) ; Spinal Cord Injuries: physiopathology (MeSH) ; Tubulin Modulators: administration & dosage (MeSH) ; Epothilones ; Tubulin Modulators ; epothilone B

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Contributing Institute(s):

1. Axon Growth and Regeneration (AG Bradke)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)

Appears in the scientific report 2015

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; IF >= 40 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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