Improved Motor Nerve Regeneration by SIRT1/Hif1a-Mediated Autophagy.
Cells
; 8(11)2019 10 30.
Article
en En
| MEDLINE
| ID: mdl-31671642
ABSTRACT
Complete restoring of functional connectivity between neurons or target tissue after traumatic lesions is still an unmet medical need. Using models of nerve axotomy and compression, we investigated the effect of autophagy induction by genetic and pharmacological manipulation on motor nerve regeneration. ATG5 or NAD+-dependent deacetylase sirtuin-1 (SIRT1) overexpression on spinal motoneurons stimulates mTOR-independent autophagy and facilitates a growth-competent state improving motor axonal regeneration with better electromyographic records after nerve transection and suture. In agreement with this, using organotypic spinal cord cultures and the human cell line SH-SY5Y, we observed that the activation of SIRT1 and autophagy by NeuroHeal increased neurite outgrowth and length extension and that this was mediated by downstream HIF1a. To conclude, SIRT1/Hifα-dependent autophagy confers a more pro-regenerative phenotype to motoneurons after peripheral nerve injury. Altogether, we provide evidence showing that autophagy induction by SIRT1/Hifα activation or NeuroHeal treatment is a novel therapeutic option for improving motor nerve regeneration and functional recovery after injury.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autofagia
/
Subunidad alfa del Factor 1 Inducible por Hipoxia
/
Sirtuina 1
/
Proteína 5 Relacionada con la Autofagia
/
Neuronas Motoras
/
Regeneración Nerviosa
/
Neuroblastoma
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cells
Año:
2019
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
CH
/
SUIZA
/
SUÍÇA
/
SWITZERLAND