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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Academic Press
2021
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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. |
format | Online Article Text |
id | pubmed-8024785 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Academic Press |
record_format | MEDLINE/PubMed |
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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