{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:33:07Z","timestamp":1788323587766,"version":"build-2803163510"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T00:00:00Z","timestamp":1667779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>\n                    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\n                    <jats:italic>c-fos<\/jats:italic>\n                    ,\n                    <jats:italic>perp<\/jats:italic>\n                    and\n                    <jats:italic>fas<\/jats:italic>\n                    in vulnerable motor neurons of SMA mice. Fluorescence\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization (FISH) of SMA motor neurons revealed\n                    <jats:italic>c-fos<\/jats:italic>\n                    RNA as a promising candidate. Accordingly, we identified p53-dependent nuclear upregulation of c-Fos protein in degenerating motor neurons from the severe\n                    <jats:italic>SMN<\/jats:italic>\n                    \u0394\n                    <jats:italic>7<\/jats:italic>\n                    and intermediate\n                    <jats:italic>\n                      Smn\n                      <jats:sup>\n                        2\n                        <jats:italic>B\/<\/jats:italic>\n                        \u2013\n                      <\/jats:sup>\n                    <\/jats:italic>\n                    SMA mouse models. Although motor neuron-specific\n                    <jats:italic>c-fos<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.3389\/fncel.2022.1038276","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T01:46:22Z","timestamp":1667785582000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["p53-dependent c-Fos expression is a marker but not executor for motor neuron death in spinal muscular atrophy mouse models"],"prefix":"10.3389","volume":"16","author":[{"given":"Jannik M.","family":"Buettner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Sowoidnich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gerstner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Blanco-Redondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hallermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian M.","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.ebiom.2019.06.013","article-title":"Aberrant axon branching via Fos-B dysregulation in FUS-ALS motor neurons.","volume":"45","author":"Akiyama","year":"2019","journal-title":"EBioMedicine"},{"key":"B2","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/j.biochi.2003.09.006","article-title":"A role for AP-1 in apoptosis: The case for and against.","volume":"85","author":"Ameyar","year":"2003","journal-title":"Biochimie"},{"key":"B3","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1101\/gad.14.6.704","article-title":"PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22\/gas3 family.","volume":"14","author":"Attardi","year":"2000","journal-title":"Genes Dev."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20191734","article-title":"Synaptic restoration by cAMP\/PKA drives activity-dependent neuroprotection to motoneurons in ALS.","volume":"217","author":"Baczyk","year":"2020","journal-title":"J. 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