α-突触核蛋白通过抑制 Wnt /β-catenin信号通路参与帕金森病发病机制

摘要

Objective To investigate the effect of α-synuclein(α-syn) on Wnt /β-catenin signaling pathway in Parkinson' s disease animal models and cell models and the possible mechanism of neuronal injury. Methods Western blotting,flow cytometry,immunofluorescence and other methods were used to detect the expression of α-synuclein and the key signal molecule GSK-3β in Wnt /β-catenin signaling pathway and its effect on cell viability at the animal and cell levels. Results The expressions of α-synuclein and p-GSK-3β in the brain tissue of α-syn transgenic mice increased significantly,compared with the control group and MPTP group(P < 0. 05) . The expression levels of α-synuclein and p-GSK-3β in SH-SY5Y cells of α-syn overexpression group were significantly higher than those in the control group and MPP + injury group,and the results were statistically significant(P < 0. 05) . The α-synuclein in the aripiprazole pretreatment group was significantly increased compared with the control group and the MPP + group. There was no significant difference in pGSK-3β between the control group and the MPP + group. The cell viability of aripiprazole pretreatment group was significantly higher than that of α-syn overexpression group,and the apoptosis rate was significantly lower than that of α-syn overexpression group,the difference was statistically significant(P < 0. 05) . Immunofluorescence showed a colocalization relationship between α-synuclein and p-GSK-3β. Conclusion α-synuclein may participate in the pathogenesis of Parkinson' s disease by inhibiting the Wnt /β-catenin signaling pathway leading to neuronal damage.%的 探讨帕金森病动物模型和细胞模型中 α-突触核蛋白与 Wnt /β-catenin 信号通路的相关关系及其导致神经元损伤的可能机制.方法 在动物水平和细胞水平上应用 western blotting 方法、 流式细胞术、 免疫荧光法等方法研究 α-synuclein 与 Wnt /β-catenin 信号通路关键信号分子 GSK-3β 的表达关系及其对细胞活性的影响.结果 α-syn 转基因小鼠脑组织中 α-synuclein、 p-GSK-3β 蛋白表达量均明显增加,与对照组和 MPTP 组相比具有统计学差异(P < 0. 05); α-syn 过表达组 SH-SY5Y 细胞中 α-synuclein、 p-GSK-3β 表达量较对照组及 MPP + 损伤组明显升高,结果具有统计学差异(P < 0. 05); 阿立哌唑预处理组 α-synuclein 较对照组及 MPP + 组明显增加,p-GSK-3β 与对照组及 MPP + 组差异不具有统计学差异; 阿立哌唑预处理组细胞活性明显高于 α-syn 过表达组,细胞凋亡率较α-syn 过表达组明显下降,差异具有统计学意义(P < 0. 05); 免疫荧光法示 α-synuclein 与 p-GSK-3β 存在共定位关系.结论 α-synuclein 可能通过抑制 Wnt /β-catenin 信号通路导致神经元损伤,从而参与帕金森病的发病机制.