Neuropeptides, small peptides found in many mammalian brain, play key roles in communicating with each other to modulate neuronal activity. Here, we reported that endogenous neuropeptide salusin-beta has neuroprotective effects on the midbrain dopamine neurons and can be used as an effective therapeutic treatment for Parkinson's disease (PD). We found that the MrgprA1 receptor mediates the neuroprotective effects of salusin-beta on the midbrain dopamine neurons. Importantly, intranasal administration of salusin-beta in a PD mouse model show the neuroprotection of dopaminergic neurons and increased the survival of midbrain dopamine neurons. Furthermore, inhibition of the salusin-beta receptor, MrgprA1, abolished the neuroprotective effects induced by salusin-beta. Taken together, these results demonstrate the novel role of salusin-beta in the central nervous system and salusin-beta can be used as a novel therapeutic to effectively treat PD. (C) 2018 Elsevier Inc. All rights reserved.