Nesfatin-1 antagonized rotenone-induced neurotoxicity in MES23.5 dopaminergic cells

• Nesfatin-1 attenuated rotenone-induced cell loss.
• Nesfatin-1 prevented rotenone-induced mitochondrial dysfunction.
• Nesfatin-1 attenuated rotenone-induced caspase-3 activation.

Nesfatin-1 is a recently identified brain–gut peptide involved in feeding and energy homeostasis. Recently, it has been proved that nesfatin-1 could exert its neuroprotective effect against subarachnoid hemorrhage-induced injury via its anti-apoptotic and anti-inflammatory properties. However, whether it has neuroprotective effect on dopamine neurons is largely unknown. In the present study, we investigated the neuroprotective effect of nesfatin-1 on rotenone-treated MES23.5 dopaminergic cells and illustrated the underlying mechanisms. Our results showed that nesfatin-1 pretreatment could significantly attenuate rotenone-induced cell loss. Further studies showed that the neuroprotective effect of nesfatin-1 against rotenone was mediated by reversing rotenone-induced mitochondrial dysfunction. Nesfatin-1 could rescue rotenone-induced mitochondrial transmembrane potential collapse and restore the function of mitochondrial respiratory chain complex I. In addition, rotenone-induced release of cytochrome C from mitochondria, ROS production and the subsequent caspase-3 activation were also attenuated by nesfatin-1 pretreatment. Our data suggested that nesfatin-1 exerted its neuroprotective effect on dopaminergic cells against rotenone by ameliorating mitochondrial dysfunction and its anti-apoptotic property. This suggested that nesfatin-1 had the potential to be considered as an aid for prevention of Parkinson's disease.