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MicroRNA-92a–CPEB3 axis protects neurons against inflammatory neurodegeneration
Neuroinflammation causes neuronal injury in multiple sclerosis (MS) and other neurological diseases. MicroRNAs (miRNAs) are important modulators of neuronal stress responses, but knowledge about their contribution to neuronal protection or damage during inflammation is limited. Here, we constructed...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10672163/ https://www.ncbi.nlm.nih.gov/pubmed/38000031 http://dx.doi.org/10.1126/sciadv.adi6855 |
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author | Winkler, Iris Engler, Jan Broder Vieira, Vanessa Bauer, Simone Liu, Yi-Hsiang Di Liberto, Giovanni Grochowska, Katarzyna M. Wagner, Ingrid Bier, Jasmina Bal, Lukas C. Rothammer, Nicola Meurs, Nina Egervari, Kristof Schattling, Benjamin Salinas, Gabriela Kreutz, Michael R. Huang, Yi-Shuian Pless, Ole Merkler, Doron Friese, Manuel A. |
author_facet | Winkler, Iris Engler, Jan Broder Vieira, Vanessa Bauer, Simone Liu, Yi-Hsiang Di Liberto, Giovanni Grochowska, Katarzyna M. Wagner, Ingrid Bier, Jasmina Bal, Lukas C. Rothammer, Nicola Meurs, Nina Egervari, Kristof Schattling, Benjamin Salinas, Gabriela Kreutz, Michael R. Huang, Yi-Shuian Pless, Ole Merkler, Doron Friese, Manuel A. |
author_sort | Winkler, Iris |
collection | PubMed |
description | Neuroinflammation causes neuronal injury in multiple sclerosis (MS) and other neurological diseases. MicroRNAs (miRNAs) are important modulators of neuronal stress responses, but knowledge about their contribution to neuronal protection or damage during inflammation is limited. Here, we constructed a regulatory miRNA–mRNA network of inflamed motor neurons by leveraging cell type–specific miRNA and mRNA sequencing of mice undergoing experimental autoimmune encephalomyelitis (EAE). We found robust induction of miR-92a in inflamed spinal cord neurons and identified cytoplasmic polyadenylation element-binding protein 3 (Cpeb3) as a key target of miR-92a–mediated posttranscriptional silencing. We detected CPEB3 repression in inflamed neurons in murine EAE and human MS. Moreover, both miR-92a delivery and Cpeb3 deletion protected neuronal cultures against excitotoxicity. Supporting a detrimental effect of Cpeb3 in vivo, neuron-specific deletion in conditional Cpeb3 knockout animals led to reduced inflammation-induced clinical disability in EAE. Together, we identified a neuroprotective miR-92a–Cpeb3 axis in neuroinflammation that might serve as potential treatment target to limit inflammation-induced neuronal damage. |
format | Online Article Text |
id | pubmed-10672163 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-106721632023-11-24 MicroRNA-92a–CPEB3 axis protects neurons against inflammatory neurodegeneration Winkler, Iris Engler, Jan Broder Vieira, Vanessa Bauer, Simone Liu, Yi-Hsiang Di Liberto, Giovanni Grochowska, Katarzyna M. Wagner, Ingrid Bier, Jasmina Bal, Lukas C. Rothammer, Nicola Meurs, Nina Egervari, Kristof Schattling, Benjamin Salinas, Gabriela Kreutz, Michael R. Huang, Yi-Shuian Pless, Ole Merkler, Doron Friese, Manuel A. Sci Adv Neuroscience Neuroinflammation causes neuronal injury in multiple sclerosis (MS) and other neurological diseases. MicroRNAs (miRNAs) are important modulators of neuronal stress responses, but knowledge about their contribution to neuronal protection or damage during inflammation is limited. Here, we constructed a regulatory miRNA–mRNA network of inflamed motor neurons by leveraging cell type–specific miRNA and mRNA sequencing of mice undergoing experimental autoimmune encephalomyelitis (EAE). We found robust induction of miR-92a in inflamed spinal cord neurons and identified cytoplasmic polyadenylation element-binding protein 3 (Cpeb3) as a key target of miR-92a–mediated posttranscriptional silencing. We detected CPEB3 repression in inflamed neurons in murine EAE and human MS. Moreover, both miR-92a delivery and Cpeb3 deletion protected neuronal cultures against excitotoxicity. Supporting a detrimental effect of Cpeb3 in vivo, neuron-specific deletion in conditional Cpeb3 knockout animals led to reduced inflammation-induced clinical disability in EAE. Together, we identified a neuroprotective miR-92a–Cpeb3 axis in neuroinflammation that might serve as potential treatment target to limit inflammation-induced neuronal damage. American Association for the Advancement of Science 2023-11-24 /pmc/articles/PMC10672163/ /pubmed/38000031 http://dx.doi.org/10.1126/sciadv.adi6855 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Neuroscience Winkler, Iris Engler, Jan Broder Vieira, Vanessa Bauer, Simone Liu, Yi-Hsiang Di Liberto, Giovanni Grochowska, Katarzyna M. Wagner, Ingrid Bier, Jasmina Bal, Lukas C. Rothammer, Nicola Meurs, Nina Egervari, Kristof Schattling, Benjamin Salinas, Gabriela Kreutz, Michael R. Huang, Yi-Shuian Pless, Ole Merkler, Doron Friese, Manuel A. MicroRNA-92a–CPEB3 axis protects neurons against inflammatory neurodegeneration |
title | MicroRNA-92a–CPEB3 axis protects neurons against inflammatory neurodegeneration |
title_full | MicroRNA-92a–CPEB3 axis protects neurons against inflammatory neurodegeneration |
title_fullStr | MicroRNA-92a–CPEB3 axis protects neurons against inflammatory neurodegeneration |
title_full_unstemmed | MicroRNA-92a–CPEB3 axis protects neurons against inflammatory neurodegeneration |
title_short | MicroRNA-92a–CPEB3 axis protects neurons against inflammatory neurodegeneration |
title_sort | microrna-92a–cpeb3 axis protects neurons against inflammatory neurodegeneration |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10672163/ https://www.ncbi.nlm.nih.gov/pubmed/38000031 http://dx.doi.org/10.1126/sciadv.adi6855 |
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