Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra (SN). Our previous study demonstrated Kukoamine A to exhibit strong neuroprotective effects through anti oxidative stress, anti-inflammation, anti-excitoxicity. In the present study, MPP+ and MPTP-induced PD models of cell and animal were used to investigate the effects of KuA on PD. Our results demonstrated that KuA ameliorated cell loss and mitochondrial membrane potential (MMP) loss, and inhibited Bax/Bcl-2 ratio and MAPKs family that were induced by MPP+. In addition, animal experiments showed that KuA improved the motor function and neuronal activity, and increased the positive cells of tyrosine hydroxylase (TH) both in substantia nigra (SN) and striatum (Str). Moreover, KuA could decrease the expression of alpha-synuclein in brain. Finally, KuA exerted apparent autophagy enhancement both in vitro and in vivo. In conclusion, KuA protected against neurotoxin-induced PD due to the apoptosis inhibition and autophagy enhancement, suggesting that KuA treatment might represent a neuroprotective treatment for PD. (C) 2017 Elsevier Ltd. All rights reserved.