Tenuigenin attenuates α-synuclein-induced cytotoxicity by down-regulating polo-like kinase 3

Jinxia Zhou, Hao-Bo Zhang, Yue Huang, Yi He, Yan Zheng, John Anderson, Wei-Ping Gai, Zhi-Gang Liang, Yong Wang, Xin-Miao Ren, Qi Wang, Xiao-Li Gong, Jian Yang, Xuan Wang, Glenda Halliday, Xiaomin Wang

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    13 Citations (Scopus)

    Abstract

    Background and aims: Tenuigenin (Ten) is a Chinese herbal extract with antioxidative and antiinflammatory effects on toxin-induced cell models of Parkinson's disease (PD); however, its effects on α-synuclein toxicity-based PD models remain unknown. α-synuclein hyperphosphorylation is a key event in PD pathogenesis and potential target of therapeutic interventions. We tested whether Ten alleviates α-synuclein-induced cytotoxicity via reducing kinases that phosphorylate α-synuclein. Methods: SH-SY5Y cells transiently transfected with wild-type or A53T mutant α-synuclein were used to evaluate the effect of Ten on the levels of α-synuclein phosphorylation-related kinases. Cells treated with 10 μM Ten for 24 h were measured for viability (proliferation and apoptosis assays) and cellular proteins harvested and fractioned. The levels of total and phosphorylated α-synuclein and five associated kinases (polo-like kinase [PLK] 1-3, casein kinase [CK] 1-2) were evaluated by Western blotting. Results: Overexpression of either wild-type or A53T mutant α-synuclein decreased cell viability and increased α-synuclein phosphorylation. Ten treatment-protected cells from this α-synuclein-induced toxicity and dramatically reduced α-synuclein phosphorylation and PLK3 (but not other kinase) levels. Conclusion: In α-synuclein cell model of PD, Ten is effective in attenuating α-synuclein-induced toxicity and α-synuclein phosphorylation probably via targeting PLK3, suggesting it could be an efficient therapeutic drug to treat α-synuclein-related neurodegeneration.

    Original languageEnglish
    Pages (from-to)688-694
    Number of pages7
    JournalCNS Neuroscience & Therapeutics
    Volume19
    Issue number9
    DOIs
    Publication statusPublished - Sep 2013

    Keywords

    • α-synuclein
    • Kinase
    • Parkinson's disease
    • Phosphorylation
    • Tenuigenin

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  • Cite this

    Zhou, J., Zhang, H-B., Huang, Y., He, Y., Zheng, Y., Anderson, J., Gai, W-P., Liang, Z-G., Wang, Y., Ren, X-M., Wang, Q., Gong, X-L., Yang, J., Wang, X., Halliday, G., & Wang, X. (2013). Tenuigenin attenuates α-synuclein-induced cytotoxicity by down-regulating polo-like kinase 3. CNS Neuroscience & Therapeutics, 19(9), 688-694. https://doi.org/10.1111/cns.12124