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)
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...
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ftdznevdb:oai:pub.dzne.de:144866 2023-10-09T21:48:49+02:00 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) Wilken, Petra DE 2017 https://pub.dzne.de/record/144866 https://pub.dzne.de/search?p=id:%22DZNE-2020-00291%22 ger ger https://pub.dzne.de/record/144866 https://pub.dzne.de/search?p=id:%22DZNE-2020-00291%22 info:eu-repo/semantics/closedAccess 63 pages : illustrations, VII (2017). = Habilitationsschrift, Georg-August-Universität zu Göttingen, 2016 info:eu-repo/semantics/doctoralThesis info:eu-repo/semantics/publishedVersion 2017 ftdznevdb 2023-09-21T07:36:27Z 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. Doctoral or Postdoctoral Thesis Arctic DZNEPUB (German Center for Neurodegenerative Diseases) Arctic |
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DZNEPUB (German Center for Neurodegenerative Diseases) |
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German |
description |
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. |
format |
Doctoral or Postdoctoral Thesis |
author |
Wilken, Petra |
spellingShingle |
Wilken, Petra 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) |
author_facet |
Wilken, Petra |
author_sort |
Wilken, Petra |
title |
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) |
title_short |
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) |
title_full |
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) |
title_fullStr |
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) |
title_full_unstemmed |
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) |
title_sort |
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) |
publishDate |
2017 |
url |
https://pub.dzne.de/record/144866 https://pub.dzne.de/search?p=id:%22DZNE-2020-00291%22 |
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DE |
geographic |
Arctic |
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Arctic |
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Arctic |
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Arctic |
op_source |
63 pages : illustrations, VII (2017). = Habilitationsschrift, Georg-August-Universität zu Göttingen, 2016 |
op_relation |
https://pub.dzne.de/record/144866 https://pub.dzne.de/search?p=id:%22DZNE-2020-00291%22 |
op_rights |
info:eu-repo/semantics/closedAccess |
_version_ |
1779311886399963136 |