| Title : Tacrine(2)-ferulic acid, a novel multifunctional dimer, attenuates 6-hydroxydopamine-induced apoptosis in PC12 cells by activating Akt pathway - Zhang_2011_Neurochem.Int_59_981 |
| Author(s) : Zhang H , Mak SH , Cui W , Li W , Han R , Hu S , Ye M , Pi R , Han YF |
| Ref : Neurochem Int , 59 :981 , 2011 |
|
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 muM) attenuated 6-OHDA-induced apoptosis in a concentration-dependent manner. The activations of glycogen synthase kinase 3beta (GSK3beta) and extracellular signal-regulated kinase (ERK) were observed after the treatment of 6-OHDA. Both SB415286 (an inhibitor of GSK3beta) and PD98059 (an inhibitor of ERK kinase) reduced the neurotoxicity induced by 6-OHDA, indicating that GSK3beta and ERK are involved in 6-OHDA-induced apoptosis. T2FA was able to inhibit the activation of GSK3beta, 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. |
| PubMedSearch : Zhang_2011_Neurochem.Int_59_981 |
| PubMedID: 21939707 |
Zhang H, Mak SH, Cui W, Li W, Han R, Hu S, Ye M, Pi R, Han YF (2011)
Tacrine(2)-ferulic acid, a novel multifunctional dimer, attenuates 6-hydroxydopamine-induced apoptosis in PC12 cells by activating Akt pathway
Neurochem Int
59 :981
Zhang H, Mak SH, Cui W, Li W, Han R, Hu S, Ye M, Pi R, Han YF (2011)
Neurochem Int
59 :981