%0 Journal Article %T Nitazoxanide, an anti-parasitic drug, efficiently ameliorates learning and memory impairments in AD model mice %J - %D 2019 %R https://doi.org/10.1038/s41401-019-0220-1 %X The pathogenesis of Alzheimer's disease (AD) is characterized by both accumulation of ¦Â-amyloid (A¦Â) plaque and formation of neurofibrillary tangles in the brain. Recent evidence shows that autophagy activation may potently promote intracellular A¦Â clearance. Thus targeting autophagy becomes a promising strategy for discovery of drug leads against AD. In the present study, we established a platform to discover autophagy stimulator and screened the lab in-house FDA-approved drug library. We found that anti-parasitic drug nitazoxanide (NTZ) was an autophagy activator and could efficiently improve learning and memory impairments in APP/PS1 transgenic mice. In BV2 cells and primary cortical astrocytes, NTZ stimulated autophagy and promoted A¦Â clearance by inhibiting both PI3K/AKT/mTOR/ULK1 and NQO1/mTOR/ULK1 signaling pathways; NTZ treatment attenuated LPS-induced inflammation by inhibiting PI3K/AKT/I¦ÊB/NF¦ÊB signaling. In SH-SY5Y cells and primary cortical neurons, NTZ treatment restrained tau hyperphosphorylation through inhibition of PI3K/AKT/GSK3¦Â pathway. The beneficial effects and related signaling mechanisms from the in vitro studies were also observed in APP/PS1 transgenic mice following administration of NTZ (90£¿mg¡¤kg£¿1¡¤d£¿1, ig) for 100 days. Furthermore, NTZ administration decreased A¦Â level and senile plaque formation in the hippocampus and cerebral cortex of APP/PS1 transgenic mice, and improved learning and memory impairments in Morris water maze assay. In conclusion, our results highlight the potential of NTZ in the treatment of AD %U https://www.nature.com/articles/s41401-019-0220-1