GSK-3β Inhibitor Alsterpaullone Attenuates MPP(+)-Induced Cell Damage in a c-Myc-Dependent Manner in SH-SY5Y Cells

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.