The Effects of Various Pharmacological Agents on the Sleep and Locomotor Activity of Drosophila Models of ALS
PublisherThe University of Arizona.
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AbstractAmyotrophic Lateral Sclerosis (ALS) is a lethal, adult-onset, progressive neurodegenerative disease in which the degeneration and death of motor neurons results in muscle weakness and paralysis throughout the body, followed by death due to respiratory failure. As a RNA-binding protein, TDP-43 has been implicated as both a cause and marker of both familial (fALS) and sporadic (sALS) cases of the disease. Our laboratory has generated a Drosophila model of ALS based on human TDP-43, which allows us to study various aspects of the disease pathology in vivo, including sleep and locomotor activity. Because pharmacological treatment of ALS is currently limited to alleviating symptoms, with severely limited effects on the increase in survival period, studies of potential therapeutics would significantly contribute to the treatment of the disease. In identifying potential candidates, 4-aminoquinoline (AAQ) has shown potential in increasing survival of Drosophila TDP-43 mutants. Using the Trikinetics Drosophila Activity Monitoring system, we examine the ability of AAQ to ameliorate defects in sleep and locomotor activity in our model. Our data indicate that AAQ can decrease sleep fragmentation, suggesting that this small molecule has the potential to be developed as a drug therapy for ALS.
Degree ProgramHonors College
Molecular and Cellular Biology