Please use this identifier to cite or link to this item: http://hdl.handle.net/2067/42944
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dc.contributor.authorRomano, Niclait
dc.contributor.authorCatalani, Alessiait
dc.contributor.authorLattante, Serenait
dc.contributor.authorBelardo,Antonioit
dc.contributor.authorProietti, Silviait
dc.contributor.authorBertini, Laurait
dc.contributor.authorSilvestri, Federicait
dc.contributor.authorCatalani, Elisabettait
dc.contributor.authorCervia, Davideit
dc.contributor.authorZolla, Lelloit
dc.contributor.authorSabatelli,Marioit
dc.contributor.authorWelshhans, Kristyit
dc.contributor.authorCeci, Marcelloit
dc.date.accessioned2021-02-22T11:44:34Z-
dc.date.available2021-02-22T11:44:34Z-
dc.date.issued2020it
dc.identifier.issn0898-6568it
dc.identifier.urihttp://hdl.handle.net/2067/42944-
dc.description.abstractThe main hallmark of many forms of familiar and sporadic amyotrophic lateral sclerosis (ALS) is a reduction in nuclear TDP-43 protein and its inclusion in cytoplasmic aggregates in motor neurons. In order to understand which cellular and molecular mechanisms underlie the mislocalization of TDP-43, we examined human skin fibroblasts from two individuals with familial ALS, both with mutations in TDP-43, and two individuals with sporadic ALS, both without TDP-43 mutations or mutations in other ALS related genes. We found that all ALS fibroblasts had a partially cytoplasmic localization of TDP-43 and had reduced cell metabolism as compared to fibroblasts from apparently healthy individuals. ALS fibroblasts showed an increase in global protein synthesis and an increase in 4E-BP1 and rpS6 phosphorylation, which is indicative of mTORC1 activity. We also observed a decrease in glutathione (GSH), which suggests that oxidative stress is elevated in ALS. ERK1/2 activity regulated the extent of oxidative stress and the localization of TDP-43 in the cytoplasm in all ALS fibroblasts. Lastly, ALS fibroblasts showed reduced stress granule formation in response to H2O2 stress. In conclusion, these findings identify specific cellular and molecular defects in ALS fibroblasts, thus providing insight into potential mechanisms that may also occur in degenerating motor neurons.it
dc.format.mediumSTAMPAit
dc.language.isoengit
dc.titleALS skin fibroblasts reveal oxidative stress and ERK1/2-mediated cytoplasmic localization of TDP-43it
dc.typearticle*
dc.identifier.doi10.1016/j.cellsig.2020.109591it
dc.identifier.pmid32126264it
dc.identifier.scopuss2.0-85081022646it
dc.identifier.urlwww.sciencedirect.com/science/article/pii/S0898656820300681?via%3Dihubit
dc.relation.journalCELLULAR SIGNALLINGit
dc.relation.firstpage1it
dc.relation.lastpage11it
dc.relation.numberofpages11it
dc.relation.article109591it
dc.relation.volume70it
dc.subject.scientificsector05-B2 / BIO 06it
dc.subject.keywordsALSit
dc.subject.keywordsERKit
dc.subject.keywordsFibroblastsit
dc.subject.keywordsOxidative stressit
dc.subject.keywordsStress granulesit
dc.subject.keywordsTDP-43it
dc.subject.ercsectorLSit
dc.description.numberofauthors13it
dc.description.internationalit
dc.contributor.countryITAit
dc.type.refereeREF_1it
dc.type.miur262it
item.fulltextWith Fulltext-
item.grantfulltextrestricted-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.openairetypearticle-
crisitem.journal.journalissn0898-6568-
crisitem.journal.anceE034040-
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