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bioRxiv · 10.1101/2025.04.24.650484

Fluphenazine, an antipsychotic compound, ameliorates Alzheimer's disease by clearing amyloid beta accumulation in

Devare, M. N.·Le, V.·Chung, V.·Vu, T.·Kaeberlein, M.
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Abstract

The ageing population worldwide faces an increasing burden of age-related conditions, with Alzheimers disease being a prominent neurodegenerative concern. Drug repurposing, the practice of identifying new therapeutic applications for existing drugs, offers a promising avenue for accelerated intervention. In this study, we utilized the yeast S. cerevisiae to screen a library of 1,760 FDA-approved compounds, both with and without rapamycin, to assess potential synergistic effects on yeast growth. We identified 87 compounds that showed synergistic effect with rapamycin and caused growth defects in yeast. These compounds were further screened for their effects on paralysis in a C. elegans model of Alzheimers disease. We found that three compounds synergistically delayed paralysis in combination with rapamycin. Additionally, four other compounds delayed paralysis when tested at different concentrations. Moreover, we tested fluphenazine, an antipsychotic drug identified in our screen and found that it enhanced the overall health of treated worms. Western blot and X-34 staining confirmed that fluphenazine reduced amyloid-beta accumulation. These results indicate that repurposed drugs have significant potential to accelerate Alzheimers disease drug discovery.

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Devare, M. N., Le, V., Chung, V., Vu, T., Kaeberlein, M.. 2025-04-26. Fluphenazine, an antipsychotic compound, ameliorates Alzheimer's disease by clearing amyloid beta accumulation in. https://doi.org/10.1101/2025.04.24.650484

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