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

• DOI: 10.1371/journal.pone.0031921
• Publication Date: 2012-02-23T22:30:16Z
• Authors: Rongbiao Pi; Xuexuan Mao; Xiaojuan Chao; Zhiyi Cheng; Mengfei Liu; Xiaolu Duan; Mingzhong Ye; Xiaohong Chen; Zhengrong Mei; Peiqing Liu; Wenming Li; Yifan Han
• Keywords: Tacrine; Pathogenesis; Amyloid (mycology)

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 they may potential pharmacological activities for treating AD. Here report first time tacrine-6-ferulic (T6FA), one these compounds, can prevent amyloid-β peptide (Aβ)-induced AD-associated pathological changes in vitro vivo. Our results showed T6FA significantly inhibited auto- acetylcholinesterase (AChE)-induced aggregation Aβ1–40 blocked cell death induced PC12 cells. In an AD mouse model intracerebroventricular injection Aβ1–40, improved cognitive ability along with increasing choline acetyltransferase superoxide dismutase activity, decreasing AChE activity malondialdehyde level. Based our findings, conclude be promising drug candidate