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Modeling Parkinson's disease in adult Drosophila
Lital Dabool1, Liza Juravlev2, Ketty Hakim-Mishnaevski2
1Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Haifa 34988, Israel; Department of Genetics and Developmental Biology, The Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, Israel.
Background:
Protein aggregation in neurons is a prominent pathological mark of neurodegeneration. In Parkinson's disease (PD), inclusions of the α-Synuclein (α-Syn) protein form the Lewy bodies in dopaminergic (DA) neurons. Ectopic expression of human α-Syn inDrosophila neurons leads to the protein accumulation, degeneration of DA neurons and locomotor deterioration, and therefore constitutes the present fly PD model. Yet, this model does not enable to study the role of genes, which are essential for normal development, in neurodegeneration.
The New Method:
Using the Gal80/Gal4/UAS system we optimized the current PD model, such that only the adult stage of the fly is affected by α-Syn expression in the brain.
Results:
The symptoms of neurodegeneration typifying the classic model, including reduced locomotor ability, shortened lifespan and the loss of DA neurons, are significantly demonstrated in the novel adult fly PD model.
Comparison With Existing Method:
The neurodegeneration symptoms exhibited by the innovative model are very similar to those manifested in the recognized one.
Conclusions:
Specific expression of α-Syn in the adult fly brain enables the investigation of developmental genes involved in neurodegeneration, thereby deciphering gene functions and molecular mechanisms. It may further be used for addressing therapeutic targets and treatment platforms specifically during adult stages.