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摘要
This study focused on a promising drug candidate, N-[2-(3,4-dimethoxyphenyl)ethyl]-3-phenyl-acrylamide (gx-50), a compound extracted from Sichuan pepper (Zanthoxylum bungeanum), to determine whether it would be an effective therapeutic for Alzheimer's disease (AD) via biological experiments. In vivo, we determined the pharmacokinetic profile of gx-50 and evaluated the effect of gx-50 on the cognitive abilities of amyloid-beta protein precursor transgenic (A beta PP-Tg) mice by Morris water maze testing. In addition, we examined the effects of gx-50 on amyloid-beta (A beta) oligomers in the brains of A beta PP-Tg mice by immunohistochemistry. In vitro, we observed a direct effect of gx-50 on A beta oligomers by atomic force microscopy, detected the neuroprotective effects of gx-50 by western blotting and cell apoptosis assays, and measured its effects on intracellular calcium currents by laser confocal microscopy. Experiments in vivo showed that gx-50 could penetrate the blood brain barrier and improve the cognitive abilities of mice. Moreover, gx-50 treatment decreased the accumulation of A beta oligomers in the cerebral cortex. The results in vitro demonstrated that gx-50 could disassemble A beta oligomers, inhibit A beta-induced neuronal apoptosis and apoptotic gene expression, and reduce neuronal calcium toxicity. These results strongly suggest that gx-50 is a potential candidate drug for treating AD.
- 出版日期2013
- 单位上海交通大学
