Drosophila Based AD & HD Models

Well characterized transgenic Drosophila models are used to screen compounds for their potential to counteract Alzheimer's or Huntington's disease related pathology.

One of the fly models was designed to screen compounds for treating Huntington’s disease. It expresses the human Huntingtin gene with a 128 poly glutamine expansion in the Drosophila CNS. This line show as striking degeneration in climbing speed over the course of a 10 day assay which can be rescued by compounds such as HDAC inhibitors.

The Alzheimer’s disease model, (APP-CT, Tau), is a double transgenic line that addresses APP cleavage, cellular trafficking, and amyloid-beta/tau interaction. Human APP-CT (C’99 APP) and human wild type Tau are co-expressed in the Drosophila cholinergic neurons. Flies expressing these transgenes exhibit a distinctive falling behavior which is tracked using an automated system (image to the right). Furthermore, the flies show evidence of plaque-like structures in aged adult brains.

The second Alzheimer’s disease model, (A-beta42, Tau), is a double transgenic line that addresses the amyloid-beta/tau interaction. Both of these human transgenes are over-expressed in the Drosophila CNS. This model shows a rapid degeneration in average speed over the course of a 14 day assay.
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