000144866 001__ 144866 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$$s1724675397_18923 000144866 3367_ $$2BibTeX$$aPHDTHESIS 000144866 3367_ $$02$$2EndNote$$aThesis 000144866 3367_ $$2DataCite$$aOutput Types/Book 000144866 3367_ $$2ORCID$$aBOOK 000144866 3367_ $$2DRIVER$$adoctoralThesis 000144866 502__ $$aHabilitationsschrift, Georg-August-Universität zu Göttingen, 2016$$bHabilitationsschrift$$cGeorg-August-Universität zu Göttingen$$d2016 000144866 520__ $$aThis study was aimed at evaluating different modulators of amyloid-beta aggregation in Drosophila melanogaster models of Alzheimer’s disease. Fly model studies are cost-effective and fast in vivo systems to screen therapeutic compounds for further testing in mouse models. Oligomers are described to be the key neurotoxic agents in neurodegenerative diseases such as Alzheimer’s disease. Previously it has been shown that anle138b, a di-phenyl-pyrazol, inhibits aggregation of prion protein and α-synuclein. We used flies expressing the arctic mutant (Glu22Gly) of amyloid beta 42 fused to a secretion signal to allow extracellular aggregation. As readout of amyloid-mediated toxicity we first expressed amyloid beta arctic in photoreceptor cells, using the UAS Gal4 System and assessed eye morphology of flies either treated with different aggregation inhibitors or solvent control. This approach captures developmental effects of amyloid beta toxicity rather than degeneration. Therefore we switched to a heat inducible expression system which allows start of expression under the neuronal elav promotor directly after hatching (elavGal4arc2e;tubGal80). We examined the influence of nine different inhibitors of aggregation on longevity compared to solvent control. The administration of the inhibitors anle138b and anle138c in the Drosophila model elavGal4/arc2e;tubGal80 showed a significantly prolonged mean survival time in contrast to the control group treated with DMSO alone. Importantly, survival of lacZ overexpression controls was not prolonged, thus excluding an unspecific effect of these compounds on the life-span. 000144866 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0 000144866 588__ $$aDataset connected to DataCite 000144866 8564_ $$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 000144866 8564_ $$uhttps://pub.dzne.de/record/144866/files/Dissertation%20Wilken%20P..pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000144866 909CO $$ooai:pub.dzne.de:144866$$popenaire$$popen_access$$pVDB$$pdriver$$pdnbdelivery 000144866 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 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$$kDZNE 000144866 9131_ $$0G:(DE-HGF)POF3-344$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lErkrankungen des Nervensystems$$vClinical and Health Care Research$$x0 000144866 920__ $$lyes 000144866 9201_ $$0I:(DE-2719)1440011$$kAG Schneider Göttingen$$lTranslational Dementia Research Göttingen$$x0 000144866 980__ $$ahabil 000144866 980__ $$aVDB 000144866 980__ $$aUNRESTRICTED 000144866 980__ $$aI:(DE-2719)1440011 000144866 9801_ $$aFullTexts