dc.contributor.advisor | Kermer, Pawel Prof. Dr. | |
dc.contributor.author | Schnieder, Marlena | |
dc.date.accessioned | 2013-11-19T11:13:48Z | |
dc.date.available | 2013-11-28T23:50:05Z | |
dc.date.issued | 2013-11-19 | |
dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0001-BC68-4 | |
dc.identifier.uri | http://dx.doi.org/10.53846/goediss-4154 | |
dc.language.iso | deu | de |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
dc.subject.ddc | 610 | de |
dc.title | Entwicklung und Evaluation eines neuen Modells für Synucleinopathien | de |
dc.type | doctoralThesis | de |
dc.title.translated | Development and evaluation of a novel model for synucleinopathy | de |
dc.contributor.referee | Kermer, Pawel Prof. Dr. | |
dc.date.examination | 2013-11-19 | |
dc.description.abstracteng | Missfolding 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.coReferee | Thumm, Michael Prof. Dr. | |
dc.subject.eng | alpha-Synuclein | de |
dc.subject.eng | aggregation | de |
dc.subject.eng | autophagy | de |
dc.subject.eng | proteasomal dysfunction | de |
dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0001-BC68-4-5 | |
dc.affiliation.institute | Medizinische Fakultät | de |
dc.subject.gokfull | Medizin (PPN619874732) | de |
dc.description.embargoed | 2013-11-28 | |
dc.identifier.ppn | 771883242 | |