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Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Identification of TBXAS1 as a candidate biomarker and potential microglia-associated inflammatory regulator in
Xiaoxue Guan1,2, Qiang Zhao3, Yong Deng4
1Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Abstract:
Parkinson's disease (PD) is a prevalent neurodegenerative disorder for which reliable biomarkers are needed to facilitate early detection and the development of targeted therapeutic strategies. Neuroinflammation has emerged as a key feature in both the initiation and progression of PD, yet the underlying regulatory networks remain incompletely understood. In this study, we integrated single-cell RNA sequencing (scRNA-seq) with bulk transcriptomic data and weighted gene co-expression network analysis (WGCNA) to identify inflammation-associated genes in PD. A PD risk score was constructed using logistic regression and LASSO, and potential functional mechanisms were explored through gene enrichment analyses. Candidate biomarker was further evaluated using in vitro cell assays and peripheral blood samples from PD patients. Our results revealed that the inflammation levels increase dynamically with disease progression and were closely associated with alterations in cellular composition. Microglia appeared to be central contributor to the inflammatory microenvironment. Among the identified genes, TBXAS1 was found to influence neuronal proliferation and apoptosis, potentially through the regulation of pro-inflammatory factor secretion in microglia. Collectively, these findings suggested that TBXAS1 may represent a candidate biomarker and potential microglia-associated inflammatory regulator in PD, providing a theoretical foundation for future studies on risk prediction and therapeutic intervention.
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