Impaired Wnt signaling in dopamine containing neurons is associated with pathogenesis in a rotenone triggered Drosophila Parkinson's disease model

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Dokumenter

DOI

  • Flora Stephano, Christian-Albrechts-Universität zu Kiel, University of Dar Es Salaam
  • ,
  • Stella Nolte
  • Julia Hoffmann, Christian-Albrechts-Universität zu Kiel, Amedon AG
  • ,
  • Samar El-Kholy, Christian-Albrechts-Universität zu Kiel, Tanta University
  • ,
  • Jakob Von Frieling, Christian-Albrechts-Universität zu Kiel
  • ,
  • Iris Bruchhaus, Bernhard Nocht Institute for Tropical Medicine
  • ,
  • Christine Fink, Christian-Albrechts-Universität zu Kiel, Airway Research Center North of the German Center for Lung Research (DZL)
  • ,
  • Thomas Roeder, Christian-Albrechts-Universität zu Kiel, Airway Research Center North of the German Center for Lung Research (DZL)

Parkinson's disease, which is the one of the most common neurodegenerative movement disorder, is characterized by a progressive loss of dopamine containing neurons. The mechanisms underlying disease initiation and development are not well understood and causative therapies are currently not available. To elucidate the molecular processes during early stages of Parkinson's disease, we utilized a Drosophila model. To induce Parkinson's disease-like phenotypes, we treated flies with the pesticide rotenone and isolated dopamine producing neurons of animals that were at an early disease stage. Transcriptomic analyses revealed that gene ontologies associated with regulation of cell death and neuronal functions were significantly enriched. Moreover, the activities of the MAPK/EGFR- and TGF-β signaling pathways were enhanced, while the Wnt pathway was dampened. In order to evaluate the role of Wnt signaling for survival of dopaminergic neurons in the disease model, we rescued the reduced Wnt signaling activity by ectopic overexpression of armadillo/β-catenin. This intervention rescued the rotenone induced movement impairments in the Drosophila model. Taken together, this initial study showed a highly relevant role of Wnt signaling for dopamine producing neurons during pathogenesis in Parkinson's disease and it implies that interfering with this pathway might by a suitable therapeutic option for the future.

OriginalsprogEngelsk
Artikelnummer2372
TidsskriftScientific Reports
Vol/bind8
Nummer1
Antal sider11
ISSN2045-2322
DOI
StatusUdgivet - 5 feb. 2018

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