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

Content Provider	Semantic Scholar
Author	Asakura, Kunihiko Ueda, Akihiro Kawamura, Naoki Ueda, Madoka Mutoh, Tatsuro
Copyright Year	2009
Abstract	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.
Starting Page	110
Ending Page	115
Page Count	6
File Format	PDF HTM / HTML
DOI	10.1016/j.brainres.2009.09.011
PubMed reference number	19748492
Journal	Medline
Volume Number	1301
Alternate Webpage(s)	https://api.elsevier.com/content/article/pii/S000689930901885X
Alternate Webpage(s)	https://www.sciencedirect.com/science/article/pii/S000689930901885X?dgcid=api_sd_search-api-endpoint
Alternate Webpage(s)	https://doi.org/10.1016/j.brainres.2009.09.011
Journal	Brain Research
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article