Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model

Reactive astrocytes have been implicated in the pathogenesis of neurodegenerative diseases, including a non-cell autonomous effect on motor neuron survival in ALS. We previously defined a mechanism by which microglia release three factors, IL-1α, TNFα, and C1q, to induce neurotoxic astrocytes. Here...

Descripción completa

Detalles Bibliográficos
Autores principales: Guttenplan, Kevin A., Weigel, Maya K., Adler, Drew I., Couthouis, Julien, Liddelow, Shane A., Gitler, Aaron D., Barres, Ben A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385161/
https://www.ncbi.nlm.nih.gov/pubmed/32719333
http://dx.doi.org/10.1038/s41467-020-17514-9
_version_ 1783563725210386432
author Guttenplan, Kevin A.
Weigel, Maya K.
Adler, Drew I.
Couthouis, Julien
Liddelow, Shane A.
Gitler, Aaron D.
Barres, Ben A.
author_facet Guttenplan, Kevin A.
Weigel, Maya K.
Adler, Drew I.
Couthouis, Julien
Liddelow, Shane A.
Gitler, Aaron D.
Barres, Ben A.
author_sort Guttenplan, Kevin A.
collection PubMed
description Reactive astrocytes have been implicated in the pathogenesis of neurodegenerative diseases, including a non-cell autonomous effect on motor neuron survival in ALS. We previously defined a mechanism by which microglia release three factors, IL-1α, TNFα, and C1q, to induce neurotoxic astrocytes. Here we report that knocking out these three factors markedly extends survival in the SOD1(G93A) ALS mouse model, providing evidence for gliosis as a potential ALS therapeutic target.
format Online
Article
Text
id pubmed-7385161
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-73851612020-08-12 Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model Guttenplan, Kevin A. Weigel, Maya K. Adler, Drew I. Couthouis, Julien Liddelow, Shane A. Gitler, Aaron D. Barres, Ben A. Nat Commun Article Reactive astrocytes have been implicated in the pathogenesis of neurodegenerative diseases, including a non-cell autonomous effect on motor neuron survival in ALS. We previously defined a mechanism by which microglia release three factors, IL-1α, TNFα, and C1q, to induce neurotoxic astrocytes. Here we report that knocking out these three factors markedly extends survival in the SOD1(G93A) ALS mouse model, providing evidence for gliosis as a potential ALS therapeutic target. Nature Publishing Group UK 2020-07-27 /pmc/articles/PMC7385161/ /pubmed/32719333 http://dx.doi.org/10.1038/s41467-020-17514-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Guttenplan, Kevin A.
Weigel, Maya K.
Adler, Drew I.
Couthouis, Julien
Liddelow, Shane A.
Gitler, Aaron D.
Barres, Ben A.
Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model
title Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model
title_full Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model
title_fullStr Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model
title_full_unstemmed Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model
title_short Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model
title_sort knockout of reactive astrocyte activating factors slows disease progression in an als mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385161/
https://www.ncbi.nlm.nih.gov/pubmed/32719333
http://dx.doi.org/10.1038/s41467-020-17514-9
work_keys_str_mv AT guttenplankevina knockoutofreactiveastrocyteactivatingfactorsslowsdiseaseprogressioninanalsmousemodel
AT weigelmayak knockoutofreactiveastrocyteactivatingfactorsslowsdiseaseprogressioninanalsmousemodel
AT adlerdrewi knockoutofreactiveastrocyteactivatingfactorsslowsdiseaseprogressioninanalsmousemodel
AT couthouisjulien knockoutofreactiveastrocyteactivatingfactorsslowsdiseaseprogressioninanalsmousemodel
AT liddelowshanea knockoutofreactiveastrocyteactivatingfactorsslowsdiseaseprogressioninanalsmousemodel
AT gitleraarond knockoutofreactiveastrocyteactivatingfactorsslowsdiseaseprogressioninanalsmousemodel
AT barresbena knockoutofreactiveastrocyteactivatingfactorsslowsdiseaseprogressioninanalsmousemodel

Ejemplares similares