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

0560416 - ÚEM 2023 RIV US eng J - Článek v odborném periodiku
van Erp, S. - van Berkel, M. - Feenstra, E.M. - Sahoo, P. K. - Wagstaff, L.J. - Twiss, J. L. - Fawcett, James - Eva, R. - Ffrench-Constant, Ch.
Age-related loss of axonal regeneration is reflected by the level of local translation.
Experimental Neurology. Roč. 339, may. (2021), č. článku 113594. ISSN 0014-4886. E-ISSN 1090-2430
Institucionální podpora: RVO:68378041
Klíčová slova: axon regeneration * human stem cells * local translation * proteomics * in vitro live imaging * axotomy
Obor OECD: Neurosciences (including psychophysiology
Impakt faktor: 5.620, rok: 2021
Způsob publikování: Open access
https://www.sciencedirect.com/science/article/pii/S0014488620304258?via%3Dihub

Regeneration capacity is reduced as CNS axons mature. Using laser-mediated axotomy, proteomics and pummycin-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.
Trvalý link: https://hdl.handle.net/11104/0333331