Targeting Vasohibins to Promote Axon Regeneration.
J Neurosci
; 44(14)2024 Apr 03.
Article
en En
| MEDLINE
| ID: mdl-38429108
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-amino-parthenolide (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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Sesquiterpenos
/
Axones
Límite:
Animals
Idioma:
En
Revista:
J Neurosci
Año:
2024
Tipo del documento:
Article
País de afiliación:
Alemania