Tacrine-6-ferulic acid, a novel multifunctional dimer, inhibits amyloid-β-mediated Alzheimer's disease-associated pathogenesis in vitro and in vivo.
Tacrine-6-ferulic acid, a novel multifunctional dimer, inhibits amyloid-β-mediated Alzheimer's disease-associated pathogenesis in vitro and in vivo.
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DOI：
10.1371/journal.pone.0031921
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Han Y
中科院分区：
文献类型：
--
作者：
Pi R;Mao X;Chao X;Cheng Z;Liu M;Duan X;Ye M;Chen X;Mei Z;Liu P;Li W;Han Y
我们先前基于阿尔茨海默病（AD）产生胆碱能缺乏和氧化应激的假设，将阿魏酸与他克林作为多功能药物连接，合成了一系列杂化化合物。有趣的是，我们发现它们可能具有治疗AD的潜在药理活性。本文首次报道了其中一种化合物他林-6-阿魏酸（T6FA）在体外和体内均能预防淀粉样蛋白-β肽（Aβ）诱导的ad相关病理改变。结果表明，T6FA可显著抑制乙酰胆碱酯酶（AChE）诱导的a - β1 - 40体外聚集，阻断a - β1 - 40诱导的PC12细胞死亡。在脑室注射a - β1 - 40的AD小鼠模型中，T6FA显著改善认知能力，增加胆碱乙酰转移酶和超氧化物歧化酶活性，降低乙酰胆碱酯酶活性和丙二醛水平。基于我们的研究结果，我们得出结论，T6FA可能是一种很有前途的多功能AD候选药物。
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-β peptide (Aβ)-induced AD-associated pathological changes in vitro and in vivo. Our results showed that T6FA significantly inhibited auto- and acetylcholinesterase (AChE)-induced aggregation of Aβ1–40 in vitro and blocked the cell death induced by Aβ1–40 in PC12 cells. In an AD mouse model by the intracerebroventricular injection of Aβ1–40, 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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影响因子：
168.9
作者：
Ballard, Clive;Gauthier, Serge;Jones, Emma
通讯作者：
Jones, Emma
影响因子：
2.1
作者：
Inestrosa, Nibaldo C.;Alvarez, Alejandra;Colombres, Marcela
通讯作者：
Colombres, Marcela
影响因子：
3.7
作者：
Bailey JA;Ray B;Greig NH;Lahiri DK
通讯作者：
Lahiri DK
影响因子：
3.8
作者：
LEBEL, CP;ALI, SF;BONDY, SC
通讯作者：
BONDY, SC
DOI：
10.1016/j.bbrc.2005.01.030
发表时间：
2005-03-25
影响因子：
3.1
作者：
Lee, KH;Shin, BH;Yu, J
通讯作者：
Yu, J