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.
|
Authors | Jin-Xia Zhou, Hao-Bo Zhang, Yue Huang, Yi He, Yan Zheng, John P Anderson, Wei-Ping Gai, Zhi-Gang Liang, Yong Wang, Xin-Miao Ren, Qi Wang, Xiao-Li Gong, Jian Yang, Xuan Wang, Glenda Halliday, Xiao-Min Wang |
Journal | CNS neuroscience & therapeutics
(CNS Neurosci Ther)
Vol. 19
Issue 9
Pg. 688-94
(Sep 2013)
ISSN: 1755-5949 [Electronic] England |
PMID | 23710708
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | © 2013 John Wiley & Sons Ltd. |
Chemical References |
- Drugs, Chinese Herbal
- Tumor Suppressor Proteins
- alpha-Synuclein
- tenuigenin
- PLK3 protein, human
- Protein Serine-Threonine Kinases
|
Topics |
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Down-Regulation
- Drugs, Chinese Herbal
(pharmacology)
- Humans
- Parkinson Disease
(drug therapy)
- Phosphorylation
- Protein Serine-Threonine Kinases
(antagonists & inhibitors)
- Tumor Suppressor Proteins
- alpha-Synuclein
(pharmacology)
|