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Improved Motor Nerve Regeneration by SIRT1/Hif1a-Mediated Autophagy

Authors
  • Romeo-Guitart, David1
  • Leiva-Rodriguez, Tatiana1
  • Forés, Joaquim
  • Casas, Caty1
  • 1 (T.L.-R.)
Type
Published Article
Journal
Cells
Publisher
MDPI AG
Publication Date
Oct 30, 2019
Volume
8
Issue
11
Identifiers
DOI: 10.3390/cells8111354
PMID: 31671642
PMCID: PMC6912449
Source
PubMed Central
Keywords
License
Green

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.

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