Alzheimer's disease: an integrative bioinformatics and machine learning analysis reveals glutamine metabolism-associated gene biomarkers.

IF 2.8 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Naifei Xing, Jingwei Yan, Rong Gao, Aihua Zhang, Huiyan He, Man Zheng, Guojing Li
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引用次数: 0

Abstract

Background: Alzheimer's disease (AD), a hallmark of age-related cognitive decline, is defined by its unique neuropathology. Metabolic dysregulation, particularly involving glutamine (Gln) metabolism, has emerged as a critical but underexplored aspect of AD pathophysiology, representing a significant gap in our current understanding of the disease.

Methods: To investigate the involvement of GlnMgs in AD, we conducted a comprehensive bioinformatic analysis. We began by identifying differentially expressed GlnMgs from a curated list of 34 candidate genes. Subsequently, we employed GSEA and GSVA to assess the biological significance of these GlnMgs. Advanced techniques such as Lasso regression and SVM-RFE were utilized to identify key hub genes and evaluate the diagnostic potential of 14 central GlnMgs in AD. Additionally, we examined their correlations with clinical parameters and validated their expression across multiple independent AD cohorts (GSE5281, GSE37263, GSE106241, GSE132903, GSE63060).

Results: Our rigorous analysis identified 14 GlnMgs-GLS2, GLS, GLUD2, GLUL, GOT1, HAL, AADAT, PFAS, ASNSD1, PPAT, NIT2, ALDH5A1, ASRGL1, and ATCAY-as potential contributors to AD pathogenesis. These genes were implicated in vital biological processes, including lipid transport and the metabolism of purine-containing compounds, in response to nutrient availability. Notably, these GlnMgs demonstrated significant diagnostic potential, highlighting their utility as both diagnostic and prognostic biomarkers for AD.

Conclusions: Our study uncovers 14 GlnMgs with potential links to AD, expanding our understanding of the disease's molecular underpinnings and offering promising avenues for biomarker development. These findings not only enhance the molecular landscape of AD but also pave the way for future diagnostic and therapeutic innovations, potentially reshaping AD diagnostics and patient care.

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来源期刊
BMC Pharmacology & Toxicology
BMC Pharmacology & Toxicology PHARMACOLOGY & PHARMACYTOXICOLOGY&nb-TOXICOLOGY
CiteScore
4.80
自引率
0.00%
发文量
87
审稿时长
12 weeks
期刊介绍: BMC Pharmacology and Toxicology is an open access, peer-reviewed journal that considers articles on all aspects of chemically defined therapeutic and toxic agents. The journal welcomes submissions from all fields of experimental and clinical pharmacology including clinical trials and toxicology.
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