Ethyl pyruvate protects SHSY5Y cells against 6-hydroxydopamine-induced neurotoxicity by upregulating autophagy.

Parkinson disease is a chronic progressive neurodegenerative disorder with a prevalence that increases with age. The glycolytic end-product pyruvate, has antioxidant and neuroprotective feature. Here, we investigated the effects of ethyl pyruvate (EP), a pyruvic acid derivative, on 6-hydroxydopamine-induced SH-SY5Y cell apoptosis. Ethyl pyruvate decreased protein levels of cleaved caspase-3, phosphorylated endoplasmic reticulum kinase (pERK), and extracellular signal-regulated kinase (ERK), suggesting that EP reduces apoptosis via the ERK signaling pathway. Ethyl pyruvate also decreased oxygen species (ROS) and neuromelanin contents, suggesting that it suppresses ROS-mediated neuromelanin synthesis. Furthermore, increased protein levels of Beclin-1 and LC-II, and LC-II:LC-I ratios indicated that EP upregulates autophagy.