Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/22759
Title: Tacrine(2)-ferulic acid, a novel multifunctional dimer, attenuates 6-hydroxydopamine-induced apoptosis in PC12 cells by activating Akt pathway
Authors: Zhang, H
Mak, S
Cui, W
Li, W
Han, R
Hu, S
Ye, M
Pi, R
Han, Y 
Keywords: 6-Hydroxydopamine
Apoptosis
Parkinson's disease
PI3-K/Akt
Tacrine(2)-ferulic acid
Issue Date: 2011
Publisher: Pergamon-Elsevier Science Ltd
Source: Neurochemistry international, 2011, v. 59, no. 7, p. 981-988 How to cite?
Journal: Neurochemistry International 
Abstract: Oxidative stress is closely related to the pathogenesis of neurodegenerative disorders such as Parkinson's disease (PD). In this study, we investigated the neuroprotective effect of tacrine-ferulic acid dimers linked by an alkylenediamine side chain (TnFA, n = 2-7), a series of novel acetylcholinesterase inhibitors, against 6-hydroxydopamine (6-OHDA)-induced apoptosis in PC12 cells. Among these dimers, pre-treatment of tacrine(2)-ferulic acid (T2FA, 3-30 μM) attenuated 6-OHDA-induced apoptosis in a concentration-dependent manner. The activations of glycogen synthase kinase 3β (GSK3β) and extracellular signal-regulated kinase (ERK) were observed after the treatment of 6-OHDA. Both SB415286 (an inhibitor of GSK3β) and PD98059 (an inhibitor of ERK kinase) reduced the neurotoxicity induced by 6-OHDA, indicating that GSK3β and ERK are involved in 6-OHDA-induced apoptosis. T2FA was able to inhibit the activation of GSK3β, but not ERK, in an Akt-dependent manner. Furthermore, LY294002, a phosphoinositide 3-kinase inhibitor, abolished the neuroprotective effect of T2FA. Collectively, these results suggest that T2FA prevents 6-OHDA-induced apoptosis possibly by activating the Akt pathway in PC12 cells.
URI: http://hdl.handle.net/10397/22759
DOI: 10.1016/j.neuint.2011.09.001
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