期刊
PLOS ONE
卷 7, 期 2, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0031921
关键词
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资金
- Fundamental Research Funds for the Central Universities [10ykpy23]
- National Natural Science Foundation of China/RGC Hong Kong [30731160617]
We have previously synthesized a series of hybrid compounds by linking ferulic acid to tacrine as multifunctional agents based on the hypotheses that Alzheimer's disease (AD) generates cholinergic deficiency and oxidative stress. Interestingly, we found that they may have potential pharmacological activities for treating AD. Here we report for the first time that tacrine-6-ferulic acid (T6FA), one of these compounds, can prevent amyloid-beta peptide (A beta)-induced AD-associated pathological changes in vitro and in vivo. Our results showed that T6FA significantly inhibited auto-and acetylcholinesterase (AChE)-induced aggregation of A beta(1-40) in vitro and blocked the cell death induced by A beta(1-40) in PC12 cells. In an AD mouse model by the intracerebroventricular injection of A beta(1-40), T6FA significantly improved the cognitive ability along with increasing choline acetyltransferase and superoxide dismutase activity, decreasing AChE activity and malondialdehyde level. Based on our findings, we conclude that T6FA may be a promising multifunctional drug candidate for AD.
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