The identification of genes causatively related to familiar forms of the disease raised the hope to identify common cellular signatures that underlie pathogenesis 7, 8. Although epidemiological and genetic studies yielded important insights into causes underlying pathogenesis, the precise pathologic molecular mechanisms remain unclear 1, 4, 5, 6.
Currently, no causative treatment strategy is available for this complex disease, where both, genetic susceptibility and environmental factors contribute to induce pathogenesis. These symptoms appear when degeneration of DA neurons is at an advanced stage. The most important symptoms are motor system disturbances such as bradykinesia, resting tremor, rigidity and postural instability. Patients suffering from PD show a selective and progressive loss of dopaminergic (DA) neurons and the presence of Lewy bodies in surviving neurons in the Substantia nigra 3. Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder with an incidence of about 1% in people older than 65 years 1, 2. 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. This intervention rescued the rotenone induced movement impairments in the Drosophila model. 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. Moreover, the activities of the MAPK/EGFR- and TGF-β signaling pathways were enhanced, while the Wnt pathway was dampened. Transcriptomic analyses revealed that gene ontologies associated with regulation of cell death and neuronal functions were significantly enriched. 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. To elucidate the molecular processes during early stages of Parkinson’s disease, we utilized a Drosophila model. The mechanisms underlying disease initiation and development are not well understood and causative therapies are currently not available.
Parkinson’s disease, which is the one of the most common neurodegenerative movement disorder, is characterized by a progressive loss of dopamine containing neurons.
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