In-vivo-Screen verschiedener Aggregationsmodulatoren in transgenen Drosophila melanogaster Alzheimermodellen

Wilken, Petra Maria Theodora Bernharda

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.identifier.uri	http://dx.doi.org/10.53846/goediss-6030
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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Human- und Zahnmedizin [2871]

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