Tacrine(2)-ferulic acid, a novel multifunctional dimer, attenuates 6-hydroxydopamine-induced apoptosis in PC12 cells by activating Akt pathway

Huan Zhang, Shinghung Mak, Wei Cui, Wenming Li, Renwen Han, Shengquan Hu, Minzhong Ye, Rongbiao Pi, Yifan Han

Research output: Journal article publicationJournal articleAcademic researchpeer-review

31 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)981-988
Number of pages8
JournalNeurochemistry International
Issue number7
Publication statusPublished - 1 Dec 2011


  • 6-Hydroxydopamine
  • Apoptosis
  • Parkinson's disease
  • PI3-K/Akt
  • Tacrine(2)-ferulic acid

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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