Tacrine-6-ferulic acid, a novel multifunctional dimer, inhibits amyloid-β-mediated Alzheimer's disease-associated pathogenesis in vitro and in vivo

Rongbiao Pi, Xuexuan Mao, Xiaojuan Chao, Zhiyi Cheng, Mengfei Liu, Xiaolu Duan, Mingzhong Ye, Xiaohong Chen, Zhengrong Mei, Peiqing Liu, Wenming Li, Yifan Han

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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.
Original languageEnglish
Article numbere31921
JournalPLoS ONE
Issue number2
Publication statusPublished - 23 Feb 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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