Abstract
SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP(+)) develop mitochondrial dysfunction and other cellular responses similar to those that occur in the dopaminergic neurons of patients with Parkinson's disease (PD). It has been shown in animal models of PD that neuronal death can be prevented by metformin, an anti-diabetic drug. Both MPP(+) and metformin inhibit complex I of the mitochondrial respiratory chain. It has been reported that decreased levels of the mitochondrial inner membrane proteins TIMM23 and NDUFS3 are associated with the increased generation of reactive oxygen species and mitochondrial depolarization. In the present study, we investigated the effects of metformin on MPP(+)-induced neurotoxicity using differentiated human SH-SY5Y neuroblastoma cells. The results showed that pretreatment with metformin increased the viability of MPP(+)-treated SH-SY5Y cells. Pretreatment with metformin decreased the expression of TIMM23 and NDUFS3 in MPP(+)-treated SH-SY5Y cells. This was correlated with reduced mitochondrial fragmentation and an improvement in the mitochondrial membrane potential. These results suggest that metformin pretreatment protects against MPP(+)-induced neurotoxicity, and offer insights into the potential role of metformin in protecting against toxin-induced parkinsonism.