Multi-omics analysis reveals the protective role of transcriptional enhancer factor and the pathogenic mechanism of monocytes in Parkinson's disease
Year: 2025
Type: article
Abstract: Parkinson's disease (PD) is a multifactorial neurodegenerative disorder whose pathogenic mechanisms remain incompletely elucidated. This study aimed to systematically identify key regulatory factors involved in PD at the genetic, cellular, and molecular levels. Using univariate Mendelian randomization (UVMR), we identified plasma proteins and genes associated with Alzheimer's disease (AD), PD, and amyotrophic lateral sclerosis (ALS), and validated their causal relationships through colocalization analysis. Cross-validation across multi-omics datasets revealed transcriptional enhancer factor (TEF) as a protective factor for PD, whereas increased counts of CD14 + CD16 + monocytes were identified as a risk factor. Single-cell analysis and multivariate Mendelian randomization (MVMR) further suggested potential mediating roles of these factors in PD pathogenesis. In vitro experiments demonstrated that TEF overexpression significantly enhanced the resistance of neuroblastoma cells to rotenone-induced damage, inhibited apoptosis, and preserved tyrosine hydroxylase (TH) expression. In vivo , TEF notably improved motor coordination and exploratory behavior in PD mouse models. Collectively, these findings suggest that TEF may exert neuroprotective effects by modulating immune and neuronal pathways, offering a novel therapeutic target for the prevention and treatment of Parkinson's disease. Protective Role of TEF in PD and the Pathogenic Mechanism of Monocytes. • This study is the first to report that Transcriptional Enhancer Factor (TEF) exerts a protective effect against Parkinson’s disease (PD) and alleviates neuronal injury. • Multi-omics causal analysis revealed a significant association between TEF and PD, suggesting TEF as a protective genetic factor. • The study identified that elevated CD14⁺CD16⁺ monocyte counts are a risk factor for PD. • Experimental results demonstrated that TEF inhibits apoptosis of SH-SY5Y cells in vitro and improves motor function in PD model mice in vivo. • These findings provide new theoretical evidence and molecular targets for the diagnosis and treatment of Parkinson’s disease.
Source: Brain Research Bulletin
Authors: Tieyi Hu, Jiazhuang Xi, Niqi Xie, Xiang Zhang, Ning Huang, Yuan Cheng
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,280
OpenAlex ID: W4415437133