Open AccessTenuigenin Attenuates α‐Synuclein‐ Induced Cytotoxicity by Down‐Regulating Polo‐Like Kinase 3
Author(s) -
Zhou JinXia,
Zhang HaoBo,
Huang Yue,
He Yi,
Zheng Yan,
Anderson John P.,
Gai WeiPing,
Liang ZhiGang,
Wang Yong,
Ren XinMiao,
Wang Qi,
Gong XiaoLi,
Yang Jian,
Wang Xuan,
Halliday Glenda,
Wang XiaoMin
Publication year - 2013
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12124
Subject(s) - kinase , phosphorylation , hyperphosphorylation , viability assay , microbiology and biotechnology , synuclein , biology , cytotoxicity , neurodegeneration , chemistry , cancer research , alpha synuclein , apoptosis , biochemistry , medicine , parkinson's disease , in vitro , disease
Summary 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.