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Identification of the mitochondria-related gene IRF7 shared by physical exercise and Parkinson's disease and exploration of its potential molecular mechanisms

bioinformatics
neuroscience
cognitive-disorders
kinesiology
data-mining-and-machine-learning

Abstract

Background. Physical exercise (PE) holds significant clinical value in improving the progression of Parkinson's disease (PD), yet its underlying regulatory mechanisms remain unclear. Our study aims to investigate the role of mitochondria-related genes in the regulatory mechanisms by which physical exercise ameliorates Parkinson's disease.

Methods. Mitochondria-related differentially expressed genes (DEGs) were screened via differentially expressed gene analysis. LASSO regression analysis and the random forest algorithm were applied for dimensionality reduction and screening of mitochondria-related hub genes. The diagnostic efficacy of mitochondria-related genes was evaluated using a nomogram model and receiver operating characteristic (ROC) curves. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and flow cytometry were employed to validate the expression of interferon regulatory factor 7 ( IRF7 ) and explore its functional mechanism in in vitro cell experiments.

Results. Our findings demonstrated that IRF7 was significantly upregulated in PD and exhibited a favorable diagnostic value (AUC = 0.875). We identified that RelA might serve as a potential transcription factor for IRF7. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated a positive correlation between IRF7 expression and the ferroptosis pathway. Additionally, PE effectively downregulated IRF7 expression. And the expression of T cell CD4 memory resting was positively correlated with IRF7 in PD. In vitro experiments showed that IRF7 can regulate intracellular lipid ROS production and expression of ferroptosis-related genes in the PD cell model.

Conclusions. PE potentially can downregulate the expression of the mitochondria-related gene IRF7, regulate the ferroptosis pathway, and thereby interfere with the progression of PD. This study provides novel insights into elucidating the potential mechanisms underlying PE-mediated prevention of PD.

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