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

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 regenerat...

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Autores principales: van Erp, Susan, van Berkel, Annemiek A., Feenstra, Eline M., Sahoo, Pabitra K., Wagstaff, Laura J., Twiss, Jeffery L., Fawcett, James W., Eva, Richard, ffrench-Constant, Charles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Academic Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024785/
https://www.ncbi.nlm.nih.gov/pubmed/33450233
http://dx.doi.org/10.1016/j.expneurol.2020.113594
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author van Erp, Susan
van Berkel, Annemiek A.
Feenstra, Eline M.
Sahoo, Pabitra K.
Wagstaff, Laura J.
Twiss, Jeffery L.
Fawcett, James W.
Eva, Richard
ffrench-Constant, Charles
author_facet van Erp, Susan
van Berkel, Annemiek A.
Feenstra, Eline M.
Sahoo, Pabitra K.
Wagstaff, Laura J.
Twiss, Jeffery L.
Fawcett, James W.
Eva, Richard
ffrench-Constant, Charles
author_sort van Erp, Susan
collection PubMed
description 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.
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spelling pubmed-80247852021-05-01 Age-related loss of axonal regeneration is reflected by the level of local translation van Erp, Susan van Berkel, Annemiek A. Feenstra, Eline M. Sahoo, Pabitra K. Wagstaff, Laura J. Twiss, Jeffery L. Fawcett, James W. Eva, Richard ffrench-Constant, Charles Exp Neurol Research Paper 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. Academic Press 2021-05 /pmc/articles/PMC8024785/ /pubmed/33450233 http://dx.doi.org/10.1016/j.expneurol.2020.113594 Text en © 2021 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
van Erp, Susan
van Berkel, Annemiek A.
Feenstra, Eline M.
Sahoo, Pabitra K.
Wagstaff, Laura J.
Twiss, Jeffery L.
Fawcett, James W.
Eva, Richard
ffrench-Constant, Charles
Age-related loss of axonal regeneration is reflected by the level of local translation
title Age-related loss of axonal regeneration is reflected by the level of local translation
title_full Age-related loss of axonal regeneration is reflected by the level of local translation
title_fullStr Age-related loss of axonal regeneration is reflected by the level of local translation
title_full_unstemmed Age-related loss of axonal regeneration is reflected by the level of local translation
title_short Age-related loss of axonal regeneration is reflected by the level of local translation
title_sort age-related loss of axonal regeneration is reflected by the level of local translation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024785/
https://www.ncbi.nlm.nih.gov/pubmed/33450233
http://dx.doi.org/10.1016/j.expneurol.2020.113594
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