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p53-dependent c-Fos expression is a marker but not executor for motor neuron death in spinal muscular atrophy mouse models
The activation of the p53 pathway has been associated with neuronal degeneration in different neurological disorders, including spinal muscular atrophy (SMA) where aberrant expression of p53 drives selective death of motor neurons destined to degenerate. Since direct p53 inhibition is an unsound the...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676941/ https://www.ncbi.nlm.nih.gov/pubmed/36419936 http://dx.doi.org/10.3389/fncel.2022.1038276 |
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author | Buettner, Jannik M. Sowoidnich, Leonie Gerstner, Florian Blanco-Redondo, Beatriz Hallermann, Stefan Simon, Christian M. |
author_facet | Buettner, Jannik M. Sowoidnich, Leonie Gerstner, Florian Blanco-Redondo, Beatriz Hallermann, Stefan Simon, Christian M. |
author_sort | Buettner, Jannik M. |
collection | PubMed |
description | The activation of the p53 pathway has been associated with neuronal degeneration in different neurological disorders, including spinal muscular atrophy (SMA) where aberrant expression of p53 drives selective death of motor neurons destined to degenerate. Since direct p53 inhibition is an unsound therapeutic approach due carcinogenic effects, we investigated the expression of the cell death-associated p53 downstream targets c-fos, perp and fas in vulnerable motor neurons of SMA mice. Fluorescence in situ hybridization (FISH) of SMA motor neurons revealed c-fos RNA as a promising candidate. Accordingly, we identified p53-dependent nuclear upregulation of c-Fos protein in degenerating motor neurons from the severe SMNΔ7 and intermediate Smn(2B/–) SMA mouse models. Although motor neuron-specific c-fos genetic deletion in SMA mice did not improve motor neuron survival or motor behavior, p53-dependent c-Fos upregulation marks vulnerable motor neurons in different mouse models. Thus, nuclear c-Fos accumulation may serve as a readout for therapeutic approaches targeting neuronal death in SMA and possibly other p53-dependent neurodegenerative diseases. |
format | Online Article Text |
id | pubmed-9676941 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96769412022-11-22 p53-dependent c-Fos expression is a marker but not executor for motor neuron death in spinal muscular atrophy mouse models Buettner, Jannik M. Sowoidnich, Leonie Gerstner, Florian Blanco-Redondo, Beatriz Hallermann, Stefan Simon, Christian M. Front Cell Neurosci Neuroscience The activation of the p53 pathway has been associated with neuronal degeneration in different neurological disorders, including spinal muscular atrophy (SMA) where aberrant expression of p53 drives selective death of motor neurons destined to degenerate. Since direct p53 inhibition is an unsound therapeutic approach due carcinogenic effects, we investigated the expression of the cell death-associated p53 downstream targets c-fos, perp and fas in vulnerable motor neurons of SMA mice. Fluorescence in situ hybridization (FISH) of SMA motor neurons revealed c-fos RNA as a promising candidate. Accordingly, we identified p53-dependent nuclear upregulation of c-Fos protein in degenerating motor neurons from the severe SMNΔ7 and intermediate Smn(2B/–) SMA mouse models. Although motor neuron-specific c-fos genetic deletion in SMA mice did not improve motor neuron survival or motor behavior, p53-dependent c-Fos upregulation marks vulnerable motor neurons in different mouse models. Thus, nuclear c-Fos accumulation may serve as a readout for therapeutic approaches targeting neuronal death in SMA and possibly other p53-dependent neurodegenerative diseases. Frontiers Media S.A. 2022-11-07 /pmc/articles/PMC9676941/ /pubmed/36419936 http://dx.doi.org/10.3389/fncel.2022.1038276 Text en Copyright © 2022 Buettner, Sowoidnich, Gerstner, Blanco-Redondo, Hallermann and Simon. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Buettner, Jannik M. Sowoidnich, Leonie Gerstner, Florian Blanco-Redondo, Beatriz Hallermann, Stefan Simon, Christian M. p53-dependent c-Fos expression is a marker but not executor for motor neuron death in spinal muscular atrophy mouse models |
title | p53-dependent c-Fos expression is a marker but not executor for motor neuron death in spinal muscular atrophy mouse models |
title_full | p53-dependent c-Fos expression is a marker but not executor for motor neuron death in spinal muscular atrophy mouse models |
title_fullStr | p53-dependent c-Fos expression is a marker but not executor for motor neuron death in spinal muscular atrophy mouse models |
title_full_unstemmed | p53-dependent c-Fos expression is a marker but not executor for motor neuron death in spinal muscular atrophy mouse models |
title_short | p53-dependent c-Fos expression is a marker but not executor for motor neuron death in spinal muscular atrophy mouse models |
title_sort | p53-dependent c-fos expression is a marker but not executor for motor neuron death in spinal muscular atrophy mouse models |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676941/ https://www.ncbi.nlm.nih.gov/pubmed/36419936 http://dx.doi.org/10.3389/fncel.2022.1038276 |
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