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000144866 005__ 20240826163725.0
000144866 0247_ $$2doi$$a10.53846/goediss-6030
000144866 037__ $$aDZNE-2020-00291
000144866 041__ $$aGerman
000144866 1001_ $$0P:(DE-2719)2814028$$aWilken, Petra$$b0$$eFirst author$$udzne
000144866 245__ $$aIn-vivo-Screen verschiedener Aggregationsmodulatoren in transgenen Drosophila melanogaster Alzheimermodellen (In-vivo-screen of different modulators of aggregation in transgenic Drosophila melanogaster models of Alzheimer's disease)$$f- 2016-12-15
000144866 260__ $$c2017
000144866 300__ $$a63 pages : illustrations, VII
000144866 3367_ $$0PUB:(DE-HGF)13$$2PUB:(DE-HGF)$$aHabil / Postdoctoral Thesis (Non-german Habil)$$bhabil$$mhabil$$s1724675397_18923
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000144866 502__ $$aHabilitationsschrift, Georg-August-Universität zu Göttingen, 2016$$bHabilitationsschrift$$cGeorg-August-Universität zu Göttingen$$d2016
000144866 520__ $$aThis 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.
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000144866 8564_ $$uhttps://ediss.uni-goettingen.de/handle/11858/00-1735-0000-002B-7D26-7
000144866 8564_ $$uhttps://pub.dzne.de/record/144866/files/Dissertation%20Wilken%20P..pdf$$yOpenAccess
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000144866 915__ $$0LIC:(DE-HGF)CCBYNCND4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0
000144866 9141_ $$y2017
000144866 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2814028$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE
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000144866 920__ $$lyes
000144866 9201_ $$0I:(DE-2719)1440011$$kAG Schneider Göttingen$$lTranslational Dementia Research Göttingen$$x0
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