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- Title
Targeting Vasohibins to Promote Axon Regeneration.
- Authors
Gobrecht, Philipp; Gebel, Jeannette; Hilla, Alexander; Gisselmann, Günter; Fischer, Dietmar
- Abstract
Treatments accelerating axon regeneration in the nervous system are still clinically unavailable. However, parthenolide promotes adult sensory neurons' axon growth in culture by inhibiting microtubule detyrosination. Here, we show that overexpression of vasohibins increases microtubule detyrosination in growth cones and compromises growth in culture and in vivo. Moreover, overexpression of these proteins increases the required parthenolide concentrations to promote axon regeneration. At the same time, the partial knockdown of endogenous vasohibins or their enhancer SVBP in neurons facilitates axon growth, verifying them as pharmacological targets for promoting axon growth. In vivo, repeated intravenous application of parthenolide or its prodrug di-methyl-aminoparthenolide (DMAPT) markedly facilitates the regeneration of sensory, motor, and sympathetic axons in injured murine and rat nerves, leading to acceleration of functional recovery. Moreover, orally applied DMAPT was similarly effective in promoting nerve regeneration. Thus, pharmacological inhibition of vasohibins facilitates axon regeneration in different species and nerves, making parthenolide and DMAPT the first promising drugs for curing nerve injury.
- Subjects
NERVOUS system regeneration; AXONS; PROTEIN overexpression; SENSORY neurons; NERVOUS system injuries
- Publication
Journal of Neuroscience, 2024, Vol 44, Issue 14, p1
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2031-23.2024