Key genes and pathways in asparagine metabolism in Alzheimer’s Disease: a bioinformatics approach

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Abstract Background Asparagine (Asn) metabolism is essential for maintaining cellular homeostasis and supporting neuronal energy demands. Recent studies have suggested its dysregulation may contribute to Alzheimer’s disease (AD) pathogenesis; however, the specific genes regulatory mechanisms involved remain incompletely understood. Methods Four publicly available microarray datasets (GSE5281, GSE29378, GSE36980, GSE138260) were utilized investigate with differential expression between control AD samples. metabolism-related (AMGs) retrieved from GeneCards database, their intersection DEGs yielded candidate asparagine differentially expressed (AMG-DEGs). Functional enrichment analysis (Gene Set Enrichment Analysis, Gene Ontology Kyoto Encyclopedia of Genes Genomes), protein–protein interaction (PPI) network analysis, centrality scoring identified hub genes. Regulatory investigated through construction competing endogenous RNA transcription factor networks. Potential therapeutic compounds predicted via drug–gene evaluated using molecular docking simulations. Results Thirty-nine AMG-DEGs found be enriched in neurodevelopmental, synaptic transmission, inflammatory signaling pathways. PPI screening revealed seven ( HPRT1 , GAD2 TUBB3 GFAP CD44 CCL2 NFKBIA ). highlighted miRNAs, long non-coding RNAs, factors modulation. Drug Bathocuproine disulfonate, DL-Mevalonic acid, Phenethyl isothiocyanate as promising strong binding affinities proteins. Conclusion This study comprehensively maps reveals a set elements potentially progression. The provide foundation further experimental validation development novel metabolism-targeted strategies treatment.

Language: Английский

Chronic Inflammation and Immune Dysregulation in Metabolic-Dysfunction-Associated Steatotic Liver Disease Progression: From Steatosis to Hepatocellular Carcinoma

Biomedicines, Journal Year: 2025, Volume and Issue: 13(5), P. 1260 - 1260

Published: May 21, 2025

Background/Objectives: Metabolic-dysfunction-associated steatotic liver disease (MASLD) progresses from hepatic steatosis to hepatocellular carcinoma (HCC) as a result of systemic immunometabolic dysfunction. This review summarizes the key roles innate and adaptive immune mechanisms driving injury, fibrogenesis, carcinogenesis in MASLD. Methods: A comprehensive literature was performed using PubMed identify relevant published studies. Eligible articles included original research clinical studies addressing immunological metabolic MASLD, well emerging therapeutic strategies. Results: We highlight cytokine networks, gut–liver axis, cell reprogramming. Emerging strategies, including inhibitors, anti-fibrotic agents, modulators, nutraceuticals, offer several indications for attenuating MASLD progression reducing prevalence extrahepatic manifestations. Conclusions: Given heterogeneity personalized combination-based approaches targeting both inflammation stress are essential effective management prevention complications.

Language: Английский