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PLoS By Category | Recent
PLoS Articles
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Biochemistry - Biotechnology - Neurological Disorders - Neuroscience - Pharmacology
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Tacrine-6-Ferulic Acid, a Novel Multifunctional Dimer, Inhibits Amyloid-ß-Mediated Alzheimer's Disease-Associated Pathogenesis In Vitro and In Vivo
Published:
Thursday, February 23, 2012
Author:
Rongbiao Pi et al.
by Rongbiao Pi, Xuexuan Mao, Xiaojuan Chao, Zhiyi Cheng, Mengfei Liu, Xiaolu Duan, Mingzhong Ye, Xiaohong Chen, Zhengrong Mei, Peiqing Liu, Wenming Li, Yifan Han
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-ß peptide (Aß)-induced AD-associated pathological changes in vitro and in vivo. Our results showed that T6FA significantly inhibited auto- and acetylcholinesterase (AChE)-induced aggregation of Aß1–40 in vitro and blocked the cell death induced by Aß1–40 in PC12 cells. In an AD mouse model by the intracerebroventricular injection of Aß1–40, 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.
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