Conclusion
Echinacoside could increase autophagy by inhibiting the expression of mTOR, thereby promoting the clearance of α-synuclein and the degradation of the autophagy substrate P62 and exerting the neuroprotective effect.
Methods
A mouse model of subacute PD was established by the intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). First, the neurobehavioral symptoms in mice of each group were evaluated, and the monoamine neurotransmitters in the striatum in each group were measured with a high-performance liquid phase. Immunofluorescence double staining was adopted to observe the expression of tyrosine hydroxylase (TH), α-synuclein, and LC3. The transmission electron microscope was used to observe the changes of ultrastructure in substantia nigra and the formation of autophagosomes. Then, the expressions of TH, α-synuclein, Beclin 1, LC3, P62, mTOR, and the up-stream protein AKT were detected by Western blot.
Objective
The present study aimed to investigate the effect of echinacoside on autophagy-related indicators through the mTOR signaling pathway, especially the effect on the clearance of autophagy substrate P62 and α-synuclein, the core pathological products of Parkinson's disease (PD), to provide new strategies for the treatment of PD.
Results
When compared with the model group, the neurobehavioral function significantly improved in the echinacoside group (P < 0.01), together with increased expression of TH, DA, and DOPAC in the brain (P < 0.01). In the echinacoside group, while the expressions of Beclin 1 and LC3-II increased (P < 0.01), the expression levels of P62 and α-synuclein decreased significantly (P < 0.01). Echinacoside could up-regulate the expression level of the survival signal p-AKT/AKT and decrease the expression of mTOR.