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Construction of Aβ42 Transgenic AD Flies and Their Applications in Drug Screening
Wang Junjie, Wang Min, Zhang Lihong, Zhang Ru*
Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and technology,Tongji University, Shanghai 200092, China
Abstract: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by generation and deposition of β-amyloid (Aβ). Aβ42 has been suggested to play a central role in the pathogenesis of AD. Fly is a well-established model system with abundant genetic tools. Using the classic Gal4/UAS system， we constructed transgenic AD flies expressing one copy or two copies of Aβ42 in all neurons or cholinergic neurons and found all transgenic AD flies showed locomotor dysfunction and shortened lifespan. Such phenotype could be reversed by Aricept， an FDA-approved AD therapeutic drug. Moreover， further tests revealed that δ-opioid receptor (DOR) antagonist naltrindole improved locomotor function and prolonged the lifespan in transgenic AD flies. Our study offers a useful tool as a preliminary drug screen model for AD therapy.
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