Drosophila Models of Parkinson's Disease: Discovering Relevant Pathways and Novel Therapeutic Strategies

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder and is mainly characterized by the selective and progressive loss of dopaminergic neurons, accompanied by locomotor defects. Although most PD cases are sporadic, several genes are associated with rare familial forms of the disease. Analyses of their function have provided important insights into the disease process, demonstrating that three types of cellular defects are mainly involved in the formation and/or progression of PD: abnormal protein aggregation, oxidative damage, and mitochondrial dysfunction. These studies have been mainly performed in PD models created in mice, fruit flies, and worms. Among them, Drosophila has emerged as a very valuable model organism in the study of either toxin-induced or genetically linked PD. Indeed, many of the existing fly PD models exhibit key features of the disease and have been instrumental to discover pathways relevant for PD pathogenesis, which could facilitate the development of therapeutic strategies.

Effects of Five Ayurvedic Herbs on Locomotor Behaviour in a Drosophila melanogaster Parkinson's Disease Model

“…This may be because in untreated WT flies, climbing ability is more or less optimal. In PINK1 flies, on the other hand, climbing ability is less than optimal owing to loss of function of PINK1, leading to muscle degeneration, hypersensitivity to oxidative stress, mitochondrial defects, reduced lifespan and degeneration of dopaminergic neurons (Muñez‐Soriano and Paricio, ). By treating PINK1 flies, one or more of these problems may be ameliorated, leading to a better ability to climb.…”

“…Our initial strategy was to first test whether these herbs may improve locomotion in a simple animal model of PD, the fruit fly (Drosophila melanogaster). Drosophila melanogaster has been extensively used to model PD (Whitworth, 2011) and provides a time-effective and cost-effective screening tool to evaluate the efficacy of potential therapeutics (Pandey and Nichols, 2011) Here, we used D. melanogaster PINK1 mutants, which show several phenotypes characteristic of PD, including dopamine neuronal degeneration and locomotor defects (Park et al, 2006;Muñez-Soriano and Paricio, 2011). Positive results with this simple model system would support the investment of further work in additional pre-clinical models.…”

The role of α-synuclein in neurodegeneration — An update

“…MPTP [738], rotenone and paraquat [739][740][741][742], and genetic. Despite [748][749][750], Caenorhabditis elegans [492,751] and in mammalians [752] have been developed to study the cellular mechanisms impaired in this disease [746].…”

Methods to Characterize Spontaneous and Startle-induced Locomotion in a Rotenone-induced Parkinson's Disease Model of <em>Drosophila</em>

“…Dopaminergic neurons are more prone to rotenone toxicity, making the effects of the chemical primarily motor based 2,7 . By inducing Parkinson's disease symptoms in flies, we can better understand the disease and remedy its symptoms 6,[8][9][10][11] . Drosophila provides a good model for studying this effect because they are genetically tractable, easy to maintain, and have a rapid life cycle.…”

“…Startle-induced locomotion plot of flies exposed to increasing doses of rotenone. Wild type, canton-S, male flies were exposed to different dosages of rotenone for 3 days and surviving flies (8)(9)(10)(11)(12) were then tapped into the bottom of the double vial apparatus. Flies exposed to 500 μM rotenone show a significant decrease in the percent of flies in the top (A) and increase in the percent of flies in the bottom section (B) of the apparatus after 30 sec.…”