Improved motor nerve regeneration by SIRT1/Hif1a-mediated autophagy

David Romeo-Guitart, Tatiana Leiva-Rodriguez, Joaquim Forés, Caty Casas*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Article number1354
Number of pages20
JournalCells
Volume8
Issue number11
DOIs
Publication statusPublished - Nov 2019

Keywords

  • Autophagy
  • Axonal regeneration
  • Motoneuron
  • Neuroheal
  • Peripheral nerve injury
  • SIRT1/hif1α

Fingerprint

Dive into the research topics of 'Improved motor nerve regeneration by SIRT1/Hif1a-mediated autophagy'. Together they form a unique fingerprint.

Cite this