Protective effect of cistanoside A on dopaminergic neurons in Parkinson's disease via mitophagy

One of the main pathological features of Parkinson's disease (PD) is the loss of dopaminergic neurons in the substantia nigra compacta (SNc). Cistanoside A (CA) has a strong neuroprotective effect in PD, but the exact mechanism is unclear. In the present study, the MPTP-stimulated mouse model of PD and MPP⁺ -treated PD model in the MES23.5 neuronal cell model of PD were used to investigate the neuroprotective effects of CA on PD and its potential mechanism. The in vivo experiment results indicated that CA improved the motor function in mice and increased the number of tyrosine hydroxylase positive cells in SNc. In vitro experiments showed that CA reduced the MPP⁺ -induced decrease in neurons and mitochondrial membrane potential and promoted the activation of autophagosomes. Furthermore, we found that CA promoted the recruitment of PINK1 and Parkin aggregation to impair mitochondrial membranes and inhibited mitochondrial damage via LC3- and p62-mediated autophagy. In conclusion, CA protects against MPTP-induced neurotoxicity in vivo and MPP⁺ -induced neurotoxicity in vitro, possibly by promoting the PINK1/Parkin/p62 pathway to accelerate the degradation of damaged mitochondria thereby reducing oxidative stress.