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首页> 外文期刊>CNS neuroscience & therapeutics. >Tenuigenin Attenuates iα‐Synuclein‐/iInduced Cytotoxicity by Down‐Regulating Polo‐Like Kinase 3
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Tenuigenin Attenuates iα‐Synuclein‐/iInduced Cytotoxicity by Down‐Regulating Polo‐Like Kinase 3

机译：Tenuigenin通过下调Polo-like激酶3减轻α-突触核蛋白诱导的​​细胞毒性。

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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.
机译：发明背景和目的Tenuigenin（Ten）是一种中草药提取物，对帕金森氏病（PD）的毒素诱导的细胞模型具有抗氧化和抗炎作用。然而，其对基于α-突触核蛋白毒性的PD模型的影响仍然未知。 α-突触核蛋白过度磷酸化是PD发病机理中的关键事件，也是治疗干预的潜在靶标。我们测试了“十”是否通过减少磷酸化α-突触核蛋白的激酶来减轻α-突触核蛋白诱导的细胞毒性。方法使用野生型或A53T突变型α-突触核蛋白瞬时转染的SH‐SY5Y细胞，评估10对α-突触核蛋白磷酸化相关激酶水平的影响。测量用10μM十号溶液处理24小时的细胞的生存能力（增殖和凋亡测定），并收获和分级分离细胞蛋白。通过蛋白质印迹法评估了总的和磷酸化的α-突触核蛋白和五个相关激酶（polo样激酶[PLK] 1-3，酪蛋白激酶[CK] 1-2）的水平。结果野生型或A53T突变型α-突触核蛋白的过表达会降低细胞活力并增加α-突触核蛋白的磷酸化。十种受治疗保护的细胞不受此α-突触核蛋白诱导的毒性影响，并显着降低了α-突触核蛋白的磷酸化和PLK3（而非其他激酶）水平。结论在PD的α-突触核蛋白细胞模型中，Ten可能通过靶向PLK3来减轻α-突触核蛋白诱导的毒性和α-突触核蛋白磷酸化，这表明它可能是治疗α-突触核蛋白相关神经变性的有效治疗药物。

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