Clioquinol inhibits NGF-induced Trk autophosphorylation and neurite outgrowth in PC12 cells

Kunihiko Asakura, Akihiro Ueda, Naoki Kawamura, Madoka Ueda, Takateru Mihara, Tatsuro Mutoh

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Clioquinol is considered to be a causative agent of subacute myelo-optico neuropathy (SMON), although the pathogenesis of SMON is yet to be elucidated. To investigate the mechanism of neurotoxicity of clioquinol, we used PC12 cell line and focused on nerve growth factor (NGF) signaling through Trk receptor, which is essential for survival and differentiation of neuronal cells. Clioquinol inhibited NGF-induced Trk autophosphorylation in a dose-dependent manner. This inhibitory activity was further confirmed by the data of the inhibition of NGF-induced mitogen-activated protein kinase (MAPK) phosphorylation, which is located in the down stream of NGF-Trk intracellular signaling pathway. Clioquinol also caused neurite retraction induced by NGF and cell death. NGF-stimulated (differentiated) cells were more vulnerable than naïve cells. These results strongly suggest that clioquinol may cause the perturbation of the intracellular survival pathway by inhibiting Trk-initiated signaling pathway.

Original languageEnglish
Pages (from-to)110-115
Number of pages6
JournalBrain Research
Publication statusPublished - 16-11-2009

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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