title: Dopamine-dependent neurodegeneration in Drosophila models of familial and sporadic Parkinson's disease.
abstract: Parkinson's disease has been found to be caused by both, genetic and environmental factors. Despite the diversity of causes involved, a convergent pathogenic mechanism might underlie the special vulnerability of dopaminergic neurons in different forms of Parkinsonism. In recent years, a number of reports have proposed dopamine as a common player responsible in the loss of dopaminergic neurons independent of its etiology. Using RNAi lines we were able to generate flies with drastically reduced dopamine levels in the dopaminergic neurons. Combining these flies with a chemically induced Parkinson model (rotenone) and a familial form of Parkinson (mutant alpha-synuclein) we were able to show a strong reduction of neurotoxicity and a protection of the dopaminergic neurons when cellular dopamine levels were reduced. These results show that dopamine homeostasis plays a central role for the susceptibility of dopaminergic neurons to environmental and genetic factors in in vivo models of Parkinson disease.
authors.affiliation: Institute of Zoology, Universitaetsstr. 31, University of Regensburg, D-93040 Regensburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Bayersdorfer
authors.forename: Aaron
authors.initials: A
authors.lastname: Voigt
authors.forename: Stephan
authors.initials: S
authors.lastname: Schneuwly
authors.forename: José A
authors.initials: JA
authors.lastname: Botella
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D012402:Rotenone / Q000633:toxicity
chemical_list: D012402:Rotenone; D004298:Dopamine