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

30 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)981-988
Number of pages8
JournalNeurochemistry International
Volume59
Issue number7
DOIs
Publication statusPublished - 1 Dec 2011

Keywords

  • 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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