Fan, Lei published the artcileNitazoxanide, an anti-parasitic drug, efficiently ameliorates learning and memory impairments in AD model mice, Name: 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, the main research area is nitazoxanide antiparasitic agent learning memory Alzheimer disease; APP/PS1 transgenic mice; Alzheimer’s disease; autophagy; inflammation; nitazoxanide.
The pathogenesis of Alzheimer′s disease (AD) is characterized by both accumulation of β-amyloid (Aβ) plaque and formation of neurofibrillary tangles in the brain. Recent evidence shows that autophagy activation may potently promote intracellular Aβ 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 inhouse 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 Aβ clearance by inhibiting both PI3K/AKT/mTOR/ULK1 and NQO1/mTOR/ULK1 signaling pathways; NTZ treatment attenuated LPS-induced inflammation by inhibiting PI3K/AKT/IκB/NFκB signaling. In SH-SY5Y cells and primary cortical neurons, NTZ treatment restrained tau hyperphosphorylation through inhibition of PI3K/AKT/GSK3β 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 Aβ 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.
Acta Pharmacologica Sinica published new progress about Alzheimer disease Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 55981-09-4 belongs to class esters-buliding-blocks, name is 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, and the molecular formula is C12H9N3O5S, Name: 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics