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Open AccessArticle

Improved Motor Nerve Regeneration by SIRT1/Hif1a-Mediated Autophagy

Institut de Neurociències (INc) and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona (UAB) & Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, E-08193 Barcelona, Spain
Hand and Peripheral Nerve Unit, Hospital Clínic i Provincial, Universitat de Barcelona, Barcelona, Spain Biotech, S.L, E-08193 Barcelona, Spain
Author to whom correspondence should be addressed.
These authors contributed equally.
Cells 2019, 8(11), 1354;
Received: 22 August 2019 / Revised: 12 October 2019 / Accepted: 29 October 2019 / Published: 30 October 2019
(This article belongs to the Section Autophagy)
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. View Full-Text
Keywords: peripheral nerve injury; axonal regeneration; motoneuron; autophagy; SIRT1/Hif1α; NeuroHeal peripheral nerve injury; axonal regeneration; motoneuron; autophagy; SIRT1/Hif1α; NeuroHeal
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Romeo-Guitart, D.; Leiva-Rodriguez, T.; Forés, J.; Casas, C. Improved Motor Nerve Regeneration by SIRT1/Hif1a-Mediated Autophagy. Cells 2019, 8, 1354.

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