Early signs of neurodegeneration in dopaminergic neurons observed in a Drosophila model of Parkinson’s disease

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder characterized by a progressive loss of dopamine-containing neurons in the Substantia nigra and the presence of so-called Lewy bodies. The mechanisms underlying disease initiation and development are poorly understood and causative therapies are currently not available. In order to gain insights into the molecular signatures of affected neurons during early stages of Parkinson’s disease, we utilized a Drosophila Parkinson model. We applied the pesticide rotenone to induce Parkinson-like phenotypes in the fly and isolated dopamine containing neurons of animals at a presymptomatic disease stage in order to elucidate their transcriptomic characteristics. In these rotenone treated neurons several gene ontologies, including regulation of cell death, were significantly enriched. Moreover, numerous signaling pathways known to be relevant for cell survival were apparently deregulated in these neurons. While the activities of the MAPK/EGFR- and TGF-β-signaling pathways were enhanced, the performance of the Wnt-pathway was dampened, which may be of central importance for their increased propensity to undergo apoptosis. Thus, further studies involving these pathways may provide new insights into the molecular events underlying pathogenesis and may lead to the identification of new targets for neuroprotective interventions. We used rotenone to induce Parkinsonism in the fly and combined this with a cDNA microarray analysis of DA neurons that were isolated using a magnetic bead based approach.