John Van Geest Centre for Brain repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
Sergio Velasco-Aviles
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández‐CSIC, San Juan de Alicante, Spain; Hospital General Universitario de Alicante, ISABIAL, Alicante, Spain
Hugo Cabedo
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández‐CSIC, San Juan de Alicante, Spain; Hospital General Universitario de Alicante, ISABIAL, Alicante, Spain
Cristina Benito
Department of Cell and Developmental Biology, University College London, London, United Kingdom
Rhona Mirsky
Department of Cell and Developmental Biology, University College London, London, United Kingdom
After nerve injury, myelin and Remak Schwann cells reprogram to repair cells specialized for regeneration. Normally providing strong regenerative support, these cells fail in aging animals, and during chronic denervation that results from slow axon growth. This impairs axonal regeneration and causes significant clinical problems. In mice, we find that repair cells express reduced c-Jun protein as regenerative support provided by these cells declines during aging and chronic denervation. In both cases, genetically restoring Schwann cell c-Jun levels restores regeneration to control levels. We identify potential gene candidates mediating this effect and implicate Shh in the control of Schwann cell c-Jun levels. This establishes that a common mechanism, reduced c-Jun in Schwann cells, regulates success and failure of nerve repair both during aging and chronic denervation. This provides a molecular framework for addressing important clinical problems, suggesting molecular pathways that can be targeted to promote repair in the PNS.
