Parkinson's disease (PD) is the second most common neurodegenerative disease in humans. The hormone alpha-melanocytestimulating hormone (alpha-MSH) has been reported to be neuroprotective in previous studies. The aim of this study is to investigate the neuroprotective effects of alpha-MSH against the neurotoxicity of 1-methyl-4-phenylpyridinium (MPP+). Our results indicated that treatment with alpha-MSH in M17 cells attenuated MPP+-induced oxidative stress, embodied by exacerbated reactive oxygen species and protein carbonyls. In addition, we found that alpha-MSH could improve mitochondrial function in M17 cells through increasing the level of adeno-sine triphosphate and mitochondrial membrane potential. Furthermore, treatment with alpha-MSH restored the reduction of cell viability and the induction of lactate dehydrogenase release induced by alpha-MSH. Importantly, Hoechst staining results indicated that alpha-MSH treatment significantly reduces the number of apoptotic cells after treatment with MPP+. Mechanically, we found that alpha-MSH prevented apoptosis signals through reducing the level of cleaved caspase-3 and attenuating cytochrome c release. All these data imply that alpha-MSH produces a protective effect in PD. (C) 2015