Tacrine-6-Ferulic Acid, a Novel Multifunctional Dimer, Inhibits Amyloid-beta-Mediated Alzheimer's Disease-Associated Pathogenesis In Vitro and In Vivo

• Type of Material: Article
• Authors: Rongbiao Pi, Sun Yat-Sen University; Xuexuan Mao, Sun Yat-Sen University; Xiaojuan Chao, Sun Yat-Sen University; Zhiyi Cheng, Sun Yat-Sen University; Mengfei Liu, Sun Yat-Sen University; Xiaolu Duan, Sun Yat-Sen University; Mingzhong Ye, Sun Yat-Sen University; Xiaohong Chen, Sun Yat-Sen University; Zhengrong Mei, Sun Yat-Sen University; Peiqing Liu, Sun Yat-Sen University; Wenming Li, Emory University; Yifan Han, Hong Kong Polytechnic University
• Language: English
• Date: 2012-02-23
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Pi et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0031921
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 7
• Issue: 2
• Start Page: e31921
• End Page: e31921
• Grant/Funding Information: This research is supported by in part by Fundamental Research Funds for the Central Universities (No 10ykpy23) and National Natural Science Foundation of China/RGC Hong Kong Joint Research Scheme (No 30731160617) to Dr. Pi.; No additional external funding received for this study.
• Keywords: Science & Technology; Multidisciplinary Sciences; IMPAIRMENT; COGNITIVE DEFICITS; TACRINE; ACETYLCHOLINESTERASE INHIBITORS; TOXICITY; FIBRILS; FERULIC ACID; MICE; Science & Technology - Other Topics; DERIVATIVES; OXIDATIVE STRESS
• Research Categories: Health Sciences, Pharmacology; Biology, Neuroscience

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-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.