Wang Jiancai, Li Yuqian, Gao Li, Yan Fengqi, Gao Guodong, Li Lihong
Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Front Cell Neurosci. 2018 Aug 30;12:283. doi: 10.3389/fncel.2018.00283. eCollection 2018.
Mitochondrial dysfunction plays significant roles in the pathogenesis of Parkinson's Disease (PD). The inactivation of c-Myc, a down-stream gene of Wnt/β-catenin signaling, may contribute to the mitochondria dysfunction. Inhibition of glycogen synthase kinase 3β (GSK-3β) with Alsterpaullone (Als) can activate the down-stream events of Wnt signaling. Here, we investigated the protective roles of Als against MPP-induced cell apoptosis in SH-SY5Y cells. The data showed that Als effectively rescued c-Myc from the MPP-induced decline via Wnt signaling. Furthermore, Als protected SH-SY5Y cells from the MPP-induced mitochondrial fission and cell apoptosis. However, the protective roles of Als were lost under β-catenin-deficient conditions. These findings indicate that Als, a GSK-3β inhibitor, attenuated the MPP-induced mitochondria-dependent apoptotic via up-regulation of the Wnt signaling.
线粒体功能障碍在帕金森病（PD）的发病机制中起重要作用。c-Myc作为Wnt/β-连环蛋白信号的下游基因，其失活可能导致线粒体功能障碍。用阿尔斯特波隆（Als）抑制糖原合酶激酶3β（GSK-3β）可激活Wnt信号的下游事件。在此，我们研究了Als对MPP诱导的SH-SY5Y细胞凋亡的保护作用。数据表明，Als通过Wnt信号有效地挽救了c-Myc免受MPP诱导的下降。此外，Als保护SH-SY5Y细胞免受MPP诱导的线粒体分裂和细胞凋亡。然而，在β-连环蛋白缺乏的条件下，Als的保护作用丧失。这些发现表明，GSK-3β抑制剂Als通过上调Wnt信号减弱了MPP诱导的线粒体依赖性凋亡。
