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dc.contributor.advisor Schneider, Anja PD Dr.
dc.contributor.author Wilken, Petra Maria Theodora Bernharda
dc.date.accessioned 2017-01-27T11:28:02Z
dc.date.available 2017-12-13T23:50:04Z
dc.date.issued 2017-01-27
dc.identifier.uri http://hdl.handle.net/11858/00-1735-0000-002B-7D26-7
dc.language.iso deu de
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc 610 de
dc.title In-vivo-Screen verschiedener Aggregationsmodulatoren in transgenen Drosophila melanogaster Alzheimermodellen de
dc.type doctoralThesis de
dc.title.translated In-vivo-screen of different modulators of aggregation in transgenic Drosophila melanogaster models of Alzheimer's disease de
dc.contributor.referee Wirths, Oliver PD Dr.
dc.date.examination 2016-12-15
dc.description.abstracteng This study was aimed at evaluating different modulators of amyloid-beta aggregation in Drosophila melanogaster models of Alzheimer’s disease. Fly model studies are cost-effective and fast in vivo systems to screen therapeutic compounds for further testing in mouse models. Oligomers are described to be the key neurotoxic agents in neurodegenerative diseases such as Alzheimer’s disease. Previously it has been shown that anle138b, a di-phenyl-pyrazol, inhibits aggregation of prion protein and α-synuclein. We used flies expressing the arctic mutant (Glu22Gly) of amyloid beta 42 fused to a secretion signal to allow extracellular aggregation. As readout of amyloid-mediated toxicity we first expressed amyloid beta arctic in photoreceptor cells, using the UAS Gal4 System and assessed eye morphology of flies either treated with different aggregation inhibitors or solvent control. This approach captures developmental effects of amyloid beta toxicity rather than degeneration. Therefore we switched to a heat inducible expression system which allows start of expression under the neuronal elav promotor directly after hatching (elavGal4arc2e;tubGal80). We examined the influence of nine different inhibitors of aggregation on longevity compared to solvent control. The administration of the inhibitors anle138b and anle138c in the Drosophila model elavGal4/arc2e;tubGal80 showed a significantly prolonged mean survival time in contrast to the control group treated with DMSO alone. Importantly, survival of lacZ overexpression controls was not prolonged, thus excluding an unspecific effect of these compounds on the life-span. de
dc.contributor.coReferee Zweckstetter, Markus Prof. Dr.
dc.subject.ger Alzheimer de
dc.subject.ger Drosophila melanogaster de
dc.subject.ger anle138b de
dc.subject.ger Demenz de
dc.subject.ger anle138c de
dc.subject.ger Oligomere de
dc.subject.ger Aggregations Hemmstoffe de
dc.subject.ger Augenphänotyp de
dc.subject.ger Lebensdauer de
dc.subject.eng anle138b de
dc.subject.eng dementia de
dc.subject.eng Drosophila melanogaster de
dc.subject.eng anle138c de
dc.subject.eng oligomer de
dc.subject.eng aggregation inhibitors de
dc.subject.eng eye morphology de
dc.subject.eng longevity de
dc.subject.eng Alzheimer´s disease de
dc.identifier.urn urn:nbn:de:gbv:7-11858/00-1735-0000-002B-7D26-7-0
dc.affiliation.institute Medizinische Fakultät de
dc.subject.gokfull Psychiatrie (PPN619876344) de
dc.description.embargoed 2017-12-13
dc.identifier.ppn 878049169

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