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Entwicklung und Evaluation eines neuen Modells für Synucleinopathien

dc.contributor.advisorKermer, Pawel Prof. Dr.
dc.contributor.authorSchnieder, Marlena
dc.date.accessioned2013-11-19T11:13:48Z
dc.date.available2013-11-28T23:50:05Z
dc.date.issued2013-11-19
dc.identifier.urihttp://hdl.handle.net/11858/00-1735-0000-0001-BC68-4
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-4154
dc.language.isodeude
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc610de
dc.titleEntwicklung und Evaluation eines neuen Modells für Synucleinopathiende
dc.typedoctoralThesisde
dc.title.translatedDevelopment and evaluation of a novel model for synucleinopathyde
dc.contributor.refereeKermer, Pawel Prof. Dr.
dc.date.examination2013-11-19
dc.description.abstractengMissfolding and oligomerization of alpha-synuclein is considered a central event in different neurodegenerative diseases like Parkinson’s disease and related disorders. As the function of alpha-synuclein is still a matter of intense research, testing for therapeutic and neuroprotective strategies relies on assessment of alpha-synuclein induced cell death and alterations in pathways involving cellular homeostasis known to be altered in synucleinopathy. To complicate the matter, even forced overexpression of alpha-synuclein in cell lines, which represent the easiest tool to screen for treatment regimens, does not induce a relevant toxicity. We generated alpha-synuclein repeat constructs fused by flexible protein linkers, which allow the oligomerization of alpha-synuclein due to spatial proximity. Overexpression of these constructs in equimolar ratio to alpha-synuclein monomers induce aggregation and exhibit a markedly increased toxicity in SH-SY5Y cells and primary hippocampal neurons. Furthermore, the alpha-synuclein repeat constructs induced proteasomal dysfunction and as well an impairment of the macroautophagy.Therefore this novel model system for synucleinopathy imitates pathophysiological alterations and offers a valuable tool to study synucleinopathy in living cells and to screen for potential treatments for Parkinson’s disease.de
dc.contributor.coRefereeThumm, Michael Prof. Dr.
dc.subject.engalpha-Synucleinde
dc.subject.engaggregationde
dc.subject.engautophagyde
dc.subject.engproteasomal dysfunctionde
dc.identifier.urnurn:nbn:de:gbv:7-11858/00-1735-0000-0001-BC68-4-5
dc.affiliation.instituteMedizinische Fakultätde
dc.subject.gokfullMedizin (PPN619874732)de
dc.description.embargoed2013-11-28
dc.identifier.ppn771883242


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