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

AbstractBACKGROUND 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.
AuthorsJin-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
JournalCNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 19 Issue 9 Pg. 688-94 (Sep 2013) ISSN: 1755-5949 [Electronic] England
PMID23710708 (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)

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