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Updated: Jul 12, 2026
Analyzing the Parkinson's Disease Mouse Model Induced by Adeno-associated Viral Vectors Encoding Human α-Synuclein
Published on: July 29, 2022
Multi-omics integration combined with multi-source weighted analysis identifies a key microRNA combination that
Guodong Wang1, Caihong Huang1, Xinxin Luo1
1Guangxi Zhuang Autonomous Region Engineering Research Center for 3D Printing in Smart Biomanufacturing and Application, Guangxi Academy of Medical Sciences, Nanning, 530021, China; Guangxi Key Laboratory of Eye Health, Department of Technical Support, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530021, China.
Background:
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by pathological aggregation of α-synuclein and selective loss of dopaminergic neurons. The molecular mechanisms involving microRNA regulation of protein homeostasis remain incompletely understood.
Methods:
We integrated single cell RNA-seq, miRNA-seq, bulk RNA-seq, weighted gene co-expression network analysis (WGCNA), and multi-source weighted data integration to screen key miRNAs and core gene modules. The candidate miRNA combination was validated in an MPP+-induced SH-SY5Y PD cell model by measuring TH, DAT, SNCA and LRRK2 using ELISA, and TUJ1 and MAP2 using immunofluorescence.
Results:
Six miRNAs (miR-194-5p, miR-95-3p, miR-1303, miR-889-3p, miR-6506-5p, miR-1287-5p) were identified. Their combined transfection restored cell viability to ∼98%, reversed PD-like morphology, reduced SNCA by ∼46% and LRRK2 by ∼51%, restored TH (∼4.4-fold) and DAT (∼3.6-fold), and induced neuronal fate transition.
Conclusions:
This six-miRNA combination modulates multiple PD-related proteins, reverses PD-like cellular phenotypes in vitro, and induces neuronal-like marker expression, providing a preliminary basis for developing potential protein-targeted therapeutic strategies for PD.
