To explore the therapeutic effects of shRNA1 and shRNA4 on Parkinson’s disease mice based on the mutation of the SNCA gene of α-synuclein

Abstract

Based on the SNCA gene mutation of α-synuclein, the therapeutic effects of shRNA1 and shRNA4 on Parkinson’s mice were explored, and the migration mechanism of α-synuclein was explored. Methods: SNCA+/+ mice were used to induce the production of α-synuclein using tuberculin pff to establish Parkinson’s mouse models. AAV-shRNA1 and AAV-shRNA4 were used to set up control and experimental groups in different brain regions and at different times. The open field test, tail suspension test and immunofluorescence were used to explore the therapeutic effect of shRNA4 and the migration mechanism of α-synuclein. Results: ShRNA4 has a significant inhibitory effect on P-α-syn in the brains of Parkinson’s mice compared to shRNA1, and it also shows significant behavioral improvement. The α-synuclein in the olfactory bulb (OB) has undergone whole-brain invasion, while the α-synuclein in the dorsal striatum (CPu) has only undergone invasion in downstream brain regions. Conclusion: Tail vein injection of shRNA4 can have a significant inhibitory effect on α-synuclein and symptomatic treatment in Parkinson’s mice, and the earlier the treatment is initiated, the better the effect.