Shisandra Decoction Alleviates Parkinson's Disease Symptoms in a Mouse Model Through PI3K/AKT/mTOR Signalling Pathway

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor deficits and the accumulation of alpha-synuclein (α-syn).
• The mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cellular processes, including autophagy, which is implicated in PD pathogenesis.

Purpose of the Study:

• To investigate the neuroprotective effects of Schisandra Decoction (Sch D) in a mouse model of Parkinson's disease (PD).
• To elucidate the underlying mechanisms of Sch D's action, focusing on the PI3K/AKT/mTOR signaling pathway and its influence on autophagy and α-synuclein aggregation.

Main Methods:

• Establishment of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model.
• Assessment of motor function using pole climbing, rotarod, and open field tests.
• Quantification of neuroprotection markers (Tyrosine hydroxylase - TH, α-synuclein) and autophagy markers (PTEN, PI3K, Akt, p-Akt, mTOR, p-mTOR, p70s6K, p62, LC3II/I) via immunohistochemistry, RT-PCR, and Western blotting.

Main Results:

• Sch D treatment significantly improved motor function in PD mice, evidenced by reduced pole climbing time and increased rotarod duration.
• Sch D administration led to increased TH protein levels and enhanced α-synuclein clearance in the brains of PD mice.
• Sch D reversed MPTP-induced alterations in the PI3K/AKT/mTOR pathway, including reduced PTEN, increased PI3K/Akt/mTOR signaling, and normalized LC3II/I and p62 levels, indicating autophagy inhibition.

Conclusions:

• Schisandra Decoction (Sch D) demonstrates significant neuroprotective effects in an MPTP-induced Parkinson's disease mouse model.
• Sch D improves motor function and reduces α-synuclein aggregation, potentially through the inhibition of autophagy via the PI3K/AKT/mTOR pathway.
• The findings suggest that Sch D's neuroprotective properties may be linked to its ability to modulate autophagy and potentially exert antioxidant effects, warranting further investigation into its antioxidant capacity.