144866 20240826163725.0 habil VDB UNRESTRICTED I:(DE-2719)1440011 FullTexts PUB:(DE-HGF)13 PUB:(DE-HGF) Habil / Postdoctoral Thesis (Non-german Habil) habil habil 1724675397_18923 BibTeX PHDTHESIS 2 EndNote Thesis DataCite Output Types/Book ORCID BOOK DRIVER doctoralThesis DZNE-2020-00291 https://ediss.uni-goettingen.de/handle/11858/00-1735-0000-002B-7D26-7 http://pub.dzne.de/record/144866/files/Dissertation%20Wilken%20P..pdf OpenAccess http://pub.dzne.de/record/144866/files/Dissertation%20Wilken%20P..pdf?subformat=pdfa pdfa OpenAccess oai:pub.dzne.de:144866 openaire open_access VDB driver dnbdelivery 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. StatID:(DE-HGF)0510 StatID OpenAccess LIC:(DE-HGF)CCBYNCND4 HGFVOC Creative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0 2017 Habilitationsschrift, Georg-August-Universität zu Göttingen, 2016 Habilitationsschrift Georg-August-Universität zu Göttingen 2016 I:(DE-588)1065079516 P:(DE-2719)2814028 Deutsches Zentrum für Neurodegenerative Erkrankungen 0 DZNE G:(DE-HGF)POF3-344 G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-300 G:(DE-HGF)POF3 G:(DE-HGF)POF DE-HGF Gesundheit Erkrankungen des Nervensystems Clinical and Health Care Research 0 63 pages : illustrations, VII Dataset connected to DataCite In-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) - 2016-12-15 doi 10.53846/goediss-6030 2017 P:(DE-2719)2814028 Wilken, Petra 0 First author dzne German G:(DE-HGF)POF3-344 344 - Clinical and Health Care Research (POF3-344) POF3-344 POF III 0 yes I:(DE-2719)1440011 AG Schneider Göttingen Translational Dementia Research Göttingen 0