title: Tacrine-6-ferulic acid, a novel multifunctional dimer, inhibits amyloid-β-mediated Alzheimer's disease-associated pathogenesis in vitro and in vivo.
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 Aβ(1-40)in vitro and blocked the cell death induced by Aβ(1-40) in PC12 cells. In an AD mouse model by the intracerebroventricular injection of Aβ(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.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China. pirb@mail.sysu.edu.cn
authors.forename: Rongbiao
authors.initials: R
authors.lastname: Pi
authors.forename: Xuexuan
authors.initials: X
authors.lastname: Mao
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chao
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Cheng
authors.forename: Mengfei
authors.initials: M
authors.lastname: Liu
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Duan
authors.forename: Mingzhong
authors.initials: M
authors.lastname: Ye
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Chen
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Mei
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
authors.forename: Wenming
authors.initials: W
authors.lastname: Li
authors.forename: Yifan
authors.initials: Y
authors.lastname: Han
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival; D003373:Coumaric Acids / Q000737:chemistry* / Q000494:pharmacology*; D019281:Dimerization; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008956:Models, Chemical; D016716:PC12 Cells; D010455:Peptides / Q000737:chemistry; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000378:metabolism; D013619:Tacrine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D003373:Coumaric Acids; D010455:Peptides; D017382:Reactive Oxygen Species; C574537:tacrine-6-ferulic acid; D013619:Tacrine; C004999:ferulic acid; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase