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Science. 2015 Apr 17;348(6232):347-52. doi: 10.1126/science.aaa2958. Epub 2015 Mar 12.

Axonal regeneration. Systemic administration of epothilone B promotes axon regeneration after spinal cord injury.

Author information

1
Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
2
The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, 1095 Northwest 14th Terrace, Miami, FL33136, USA.
3
Spinal Cord Injury Center, Heidelberg University Hospital, Schlierbacher Landstr. 200A, 69118 Heidelberg, Germany.
4
Institute for Neuropathology, RWTH Aachen University, Steinbergweg 20, 52074, Aachen, Germany. Jülich-Aachen Research Alliance-Translational Brain Medicine.
5
Institute of Reconstructive Neurobiology, Life&Brain Center, University of Bonn and Hertie Foundation, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
6
Departments of Pathology, Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL 33101, USA.
7
Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany. frank.bradke@dzne.de.

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.

PMID:
25765066
PMCID:
PMC4445125
DOI:
10.1126/science.aaa2958
[Indexed for MEDLINE]
Free PMC Article

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