Journal article

Delaying histone deacetylase response to injury accelerates conversion into repair Schwann cells and nerve regeneration

  • Brügger, Valérie Department of Biology, University of Fribourg, Switzerland
  • Duman, Mert Department of Biology, University of Fribourg, Switzerland
  • Bochud, Maëlle Department of Biology, University of Fribourg, Switzerland
  • Münger, Emmanuelle Department of Biology, University of Fribourg, Switzerland
  • Heller, Manfred Proteomics and Mass Spectrometry Core Facility,Department of Clinical Research, University of Bern, Switzerland
  • Ruff, Sophie Department of Biology, University of Fribourg, Switzerland
  • Jacob, Claire Department of Biology, University of Fribourg, Switzerland
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    31.01.2017
Published in:
  • Nature Communications. - 2017, vol. 8, p. 14272
English The peripheral nervous system (PNS) regenerates after injury. However, regeneration is often compromised in the case of large lesions, and the speed of axon reconnection to their target is critical for successful functional recovery. After injury, mature Schwann cells (SCs) convert into repair cells that foster axonal regrowth, and redifferentiate to rebuild myelin. These processes require the regulation of several transcription factors, but the driving mechanisms remain partially understood. Here we identify an early response to nerve injury controlled by histone deacetylase 2 (HDAC2), which coordinates the action of other chromatin-remodelling enzymes to induce the upregulation of Oct6, a key transcription factor for SC development. Inactivating this mechanism using mouse genetics allows earlier conversion into repair cells and leads to faster axonal regrowth, but impairs remyelination. Consistently, short-term HDAC1/2 inhibitor treatment early after lesion accelerates functional recovery and enhances regeneration, thereby identifying a new therapeutic strategy to improve PNS regeneration after lesion.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/305428
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