Repository logo

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

Published version



Change log


van Erp, Susan 
van Berkel, Annemiek A 
Feenstra, Eline M 
Sahoo, Pabitra K 
Wagstaff, Laura J 


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.



Axon regeneration, Axotomy, Human stem cells, In vitro live imaging, Local translation, Proteomics, Axons, Cellular Senescence, Coculture Techniques, Embryonic Stem Cells, Humans, Nerve Regeneration, Protein Biosynthesis

Journal Title

Exp Neurol

Conference Name

Journal ISSN


Volume Title



Elsevier BV
Medical Research Council (MR/R004463/1)
Social Sciences and Humanities Research Council of Canada (SSHRC) (via McGill University) (Unknown)
Medical Research Council (G0300336)
International Foundation for Research in Paraplegia (IRP) (P172)
Medical Research Council (MR/R004544/1)
MRC (MR/V002694/1)