Age-related loss of axonal regeneration is reflected by the level of local translation

Susan van Erp, Annemiek A. van Berkel, Eline M. Feenstra, Pabitra K. Sahoo, Laura J. Wagstaff, Jeffery L. Twiss, James W. Fawcett, Richard Eva, Charles ffrench-Constant

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
1 Downloads (Pure)

Abstract

Regeneration capacity is reduced as CNS axons mature. Using laser-mediated axotomy, proteomics and puromycin-based tagging of newly-synthesized proteins in a human embryonic stem cell-derived neuron culture system that allows isolation of axons from cell bodies, we show here that efficient regeneration in younger axons (d45 in culture) is associated with local axonal protein synthesis (local translation). Enhanced regeneration, promoted by co-culture with human glial precursor cells, is associated with increased axonal synthesis of proteins, including those constituting the translation machinery itself. Reduced regeneration, as occurs with the maturation of these axons by d65 in culture, correlates with reduced levels of axonal proteins involved in translation and an inability to respond by increased translation of regeneration promoting axonal mRNAs released from stress granules. Together, our results provide evidence that, as in development and in the PNS, local translation contributes to CNS axon regeneration.

Original languageEnglish
Article number113594
JournalExperimental Neurology
Volume339
Early online date13 Jan 2021
DOIs
Publication statusPublished - May 2021

Keywords

  • Axon regeneration
  • Axotomy
  • Human stem cells
  • In vitro live imaging
  • Local translation
  • Proteomics

Cite this