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Iron-mediated aggregation and toxicity in a novel neuronal cell culture model with inducible alpha-synuclein expression

dc.contributor.authorBartels, Martin
dc.contributor.authorWeckbecker, Daniel
dc.contributor.authorKuhn, Peer-Hendrik
dc.contributor.authorRyazanov, Sergey
dc.contributor.authorLeonov, Andrei
dc.contributor.authorGriesinger, Christian
dc.contributor.authorLichtenthaler, Stefan F.
dc.contributor.authorBötzel, Kai
dc.contributor.authorGiese, Armin
dc.date.accessioned2019-08-07T12:43:46Z
dc.date.available2019-08-07T12:43:46Z
dc.date.issued2019de
dc.relation.ISSN2045-2322de
dc.identifier.urihttp://resolver.sub.uni-goettingen.de/purl?gs-1/16341
dc.description.abstractParkinson’s disease (PD) represents an increasing problem in society. The oligomerization of alphasynuclein (αSyn) is a suggested key event in its pathogenesis, yet the pathological modes of action remain to be fully elucidated. To identify potential disease-modifying therapeutics and to study αSynmediated toxic mechanisms, we established cell lines with inducible overexpression of different αSyn constructs: αSyn, αSyn coupled to the fluorescence protein Venus (αSyn-Venus), and αSyn coupled to the N-terminal or C-terminal part of Venus (V1S and SV2, respectively) for a bimolecular fluorescence complementation assay (BiFC). Inducibility was achieved by applying modified GAL4-UAS or Cre-loxP systems and addition of tebufenozide or 4-OH-tamoxifen, respectively. Expression constructs were stably integrated into the host genome of H4 neuroglioma cells by lentiviral transduction. We here demonstrate a detailed investigation of the expression characteristics of inducible H4 cells showing low background expression and high inducibility. We observed increased protein load and aggregation of αSyn upon incubation with DMSO and FeCl3 along with an increase in cytotoxicity. In summary, we present a system for the creation of inducibly αSyn-overexpressing cell lines holding high potential for the screening for modulators of αSyn aggregation and αSyn-mediated toxicity.de
dc.language.isoengde
dc.rightsopenAccess
dc.rights.uriresolver.sub.uni-goettingen.de/purl?gs-1/16340
dc.subjectalphasynuclein expression; neuronal cellde
dc.subject.ddc573
dc.subject.ddc612
dc.titleIron-mediated aggregation and toxicity in a novel neuronal cell culture model with inducible alpha-synuclein expressionde
dc.typejournalArticlede
dc.identifier.doi10.1038/s41598-019-45298-6
dc.type.versionpublishedVersionde
dc.relation.eISSN2045-2322
dc.bibliographicCitation.volume9de
dc.bibliographicCitation.issue1de
dc.type.subtypejournalArticle
dc.bibliographicCitation.articlenumber9100de
dc.description.statuspeerReviewedde
dc.bibliographicCitation.journalScientific Reportsde


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