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@PHDTHESIS{Wilken:144866,
      author       = {Wilken, Petra},
      title        = {{I}n-vivo-{S}creen verschiedener {A}ggregationsmodulatoren
                      in transgenen {D}rosophila melanogaster {A}lzheimermodellen
                      ({I}n-vivo-screen of different modulators of aggregation in
                      transgenic {D}rosophila melanogaster models of {A}lzheimer's
                      disease)},
      school       = {Georg-August-Universität zu Göttingen},
      type         = {Habilitationsschrift},
      reportid     = {DZNE-2020-00291},
      pages        = {63 pages : illustrations, VII},
      year         = {2017},
      note         = {Habilitationsschrift, Georg-August-Universität zu
                      Göttingen, 2016},
      abstract     = {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.},
      cin          = {AG Schneider Göttingen},
      cid          = {I:(DE-2719)1440011},
      pnm          = {344 - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)13},
      doi          = {10.53846/goediss-6030},
      url          = {https://pub.dzne.de/record/144866},
}