Sinomenine exerts a neuroprotective effect on PD mouse model through inhibiting PI3K/AKT/mTOR pathway to enhance autophagy.

Parkinson's disease (PD), as a chronic and progressive neurodegenerative disease, is associated with autophagy. This study focused on the regulation of sinomenine (SN) on autophagy in PD and its related mechanism. The PD mouse model was constructed by MPTP inducement, and the mouse motor function after modeling and SN treatment was examined by rotarod, grip strength, and foot printing tests. Tyrosine hydroxylase (TH)/LC3B-positive neurons in the substantia nigra pars compacta of mouse brains were detected by immunofluorescence. The expressions of proteins related to autophagy (Beclin1, p62, LC3-I and LC3-II) and phosphorylated phosphoinositide 3-kinase (PI3K)/AKT/mechanistic target of rapamycin kinase (mTOR) signaling pathway were measured by western blot. Rescue experiments were performed to determine the effects of MHY1485 (mTOR activator) on SN-treated PD mice. SN potentiated the motor ability in PD mice, promoted the survival of dopaminergic neurons, increased the protein expression level of Beclin1, LC3-II/LC3-I ratio and LC3B-positive neurons, lowered the protein expression level of p62 and inactivated PI3K/AKT/mTOR pathway in the substantia nigra tissue of mouse brains. Moreover, MHY1485 reversed the above effects of SN on PD mice via reactivating PI3K/AKT/mTOR pathway. SN augments the autophagy of dopaminergic neurons via inhibiting the PI3K/AKT/mTOR pathway and exerts a neuroprotective effect on PD mice. [ABSTRACT FROM AUTHOR]