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

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 ?-synuclein toxicity-based PD models remain unknown. ?-synuclein hyperphosphorylation is a key event in PD pathogenesis and potential target of therapeutic interventions. We tested whether Ten alleviates ?-synuclein-induced cytotoxicity via reducing kinases that phosphorylate ?-synuclein.

Methods

SH-SY5Y cells transiently transfected with wild-type or A53T mutant ?-synuclein were used to evaluate the effect of Ten on the levels of ?-synuclein phosphorylation-related kinases. Cells treated with 10 ?M Ten for 24 h were measured for viability (proliferation and apoptosis assays) and cellular proteins harvested and fractioned. The levels of total and phosphorylated ?-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 ?-synuclein decreased cell viability and increased ?-synuclein phosphorylation. Ten treatment-protected cells from this ?-synuclein-induced toxicity and dramatically reduced ?-synuclein phosphorylation and PLK3 (but not other kinase) levels.

Conclusion

In ?-synuclein cell model of PD, Ten is effective in attenuating ?-synuclein-induced toxicity and ?-synuclein phosphorylation probably via targeting PLK3, suggesting it could be an efficient therapeutic drug to treat ?-synuclein-related neurodegeneration.

SUBMITTER: Zhou JX 

PROVIDER: S-EPMC6493467 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature