tacrine-6-ferulic acid, a novel multifunctional dimer, inhibits amyloid-β-mediated alzheimers disease-associated pathogenesis in vitro and in vivotacrine-6-ferulic酸,一种新型多功能二聚体,抑制amyloid-β-mediated阿尔茨海默疾病有关的发病机制在体外和体内.pdfVIP

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tacrine-6-ferulic acid, a novel multifunctional dimer, inhibits amyloid-β-mediated alzheimers disease-associated pathogenesis in vitro and in vivotacrine-6-ferulic酸,一种新型多功能二聚体,抑制amyloid-β-mediated阿尔茨海默疾病有关的发病机制在体外和体内.pdf

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tacrine-6-ferulic acid, a novel multifunctional dimer, inhibits amyloid-β-mediated alzheimers disease-associated pathogenesis in vitro and in vivotacrine-6-ferulic酸,一种新型多功能二聚体,抑制amyloid-β-mediated阿尔茨海默疾病有关的发病机制在体外和体内

Tacrine-6-Ferulic Acid, a Novel Multifunctional Dimer, Inhibits Amyloid-b-Mediated Alzheimer’s Disease- Associated Pathogenesis In Vitro and In Vivo 1 1¤ 1 1 1 1 Rongbiao Pi *, Xuexuan Mao , Xiaojuan Chao , Zhiyi Cheng , Mengfei Liu , Xiaolu Duan , Mingzhong 1 2 1 1 3,4 3 Ye , Xiaohong Chen , Zhengrong Mei , Peiqing Liu , Wenming Li *, Yifan Han * 1 Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China, 2 Department of Neurology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China, 3 Department of Applied Biology and Chemical Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University, Hong Kong, China, 4 Department of Pharmacology and Neurology, School of Medicine, Emory University, Atlanta, Georgia, United States of America Abstract 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-b peptide (Ab)-induced AD-associated pathological changes in vitro and in vivo. Our results showed that T6FA significantly inhibited auto- and acetylcholinesterase (AChE)-induced aggregation of Ab1–40 in vitro and blocked the cell death induced by Ab1–40 in PC12 cells. In an AD mouse