Neuroprotective effects of Kukoamine A on neurotoxin-induced Parkinson's model through apoptosis inhibition and autophagy enhancement

- It was the first time to report that KuA have effects on PD both in vitro and in vivo.
- It was the first time to report that KuA could induce autophagy both in vitro and in vivo.
- The action mechanisms of KuA on PD were involved in multiple signalling pathways.
- KuA might be a promising neuroprotective agent for the prevention of PD.

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 α-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.

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