title: Tenuigenin attenuates α-synuclein-induced cytotoxicity by down-regulating polo-like kinase 3.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing, China.
authors.forename: Jin-Xia
authors.initials: JX
authors.lastname: Zhou
authors.forename: Hao-Bo
authors.initials: HB
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.forename: Yi
authors.initials: Y
authors.lastname: He
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.forename: John P
authors.initials: JP
authors.lastname: Anderson
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Gai
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Liang
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Xin-Miao
authors.initials: XM
authors.lastname: Ren
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Gong
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.forename: Glenda
authors.initials: G
authors.lastname: Halliday
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D025521:Tumor Suppressor Proteins; D051844:alpha-Synuclein / Q000494:pharmacology*; D000097868:Polo-like Kinases
chemical_list: D004365:Drugs, Chinese Herbal; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; D051844:alpha-Synuclein; C493220:tenuigenin; C486256:PLK3 protein, human; D000097868:Polo-like Kinases
keywords: Kinase; Parkinson's disease; Phosphorylation; Tenuigenin; α-synuclein