Apolipoprotein E in Alzheimer’s disease: molecular insights and therapeutic opportunities DOI Creative Commons
Abdel A. Belaidi, Ashley I. Bush, Scott Ayton

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: April 24, 2025

Abstract Apolipoprotein E ( APOE- gene; apoE- protein) is the strongest genetic modulator of late-onset Alzheimer’s disease (AD), with its three major isoforms conferring risk for ε2 < ε3 ε4. Emerging protective gene variants, such as APOE Christchurch and COLBOS variant REELIN , an alternative target certain apoE receptors, offer novel insights into resilience against AD. In recent years, role has been shown to extend beyond primary function in lipid transport, influencing multiple biological processes, including amyloid-β (Aβ) aggregation, tau pathology, neuroinflammation, autophagy, cerebrovascular integrity protection from peroxidation resulting ferroptotic cell death. While detrimental influence ε4 on these other processes well described, molecular mechanisms underpinning this disadvantage require further enunciation, particularly realize therapeutic opportunities related apoE. This review explores multifaceted roles AD pathogenesis, emphasizing discoveries translational approaches apoE-mediated pathways. These findings underscore potential apoE-based strategies prevent or mitigate genetically at-risk populations.

Language: Английский

Integrating single-cell and bulk RNA-seq to reveal cholesterol homeostasis-related genes via machine learning to predict prognosis and therapeutic response in hepatocellular carcinoma DOI

Xiaozhen Ji,

Wei Wang, Ke Wu

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Abstract Background: Liver cancer, particularly hepatocellular carcinoma (HCC), has emerged as a significant global health challenge. Recent studies have highlighted cholesterol homeostasis (CH) new research frontier, providing insights into its involvement in diverse biological functions and diseases. This study seeks to investigate the significance of CH context HCC. Methods: This explores CH's role HCC using single-cell RNA sequencing data (GSE140228) from TISCH database, analyzed via "Seurat" R package. Genes associated with were sourced MsigDB database. Utilizing these CH-related genes, we performed unsupervised hierarchical clustering analysis stratify (HCC) molecular subtypes. A comprehensive was conducted on differences among identified clusters, focusing clinical characteristics, pathways, infiltration immune cells. By leveraging score computed various machine learning techniques predict overall survival patients Results: We began by investigating subsequently identifying three distinct risk model developed classify high-score low-score groups. Evaluation tumor microenvironment (TIME) demonstrated that individuals categorized high-risk subgroup showed significantly reduced rates diminished therapeutic efficacy response checkpoint inhibitor treatment regimens. ANXA5, ADH4, ATXN2, ACTG1, MVD, S100A11 essential genes Conclusion: We signature derived offers strong prediction outcomes responses immunotherapy

Language: Английский

Citations

0
Apolipoprotein E in Alzheimer’s disease: molecular insights and therapeutic opportunities DOI Creative Commons
Abdel A. Belaidi, Ashley I. Bush, Scott Ayton

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: April 24, 2025

Abstract Apolipoprotein E ( APOE- gene; apoE- protein) is the strongest genetic modulator of late-onset Alzheimer’s disease (AD), with its three major isoforms conferring risk for ε2 < ε3 ε4. Emerging protective gene variants, such as APOE Christchurch and COLBOS variant REELIN , an alternative target certain apoE receptors, offer novel insights into resilience against AD. In recent years, role has been shown to extend beyond primary function in lipid transport, influencing multiple biological processes, including amyloid-β (Aβ) aggregation, tau pathology, neuroinflammation, autophagy, cerebrovascular integrity protection from peroxidation resulting ferroptotic cell death. While detrimental influence ε4 on these other processes well described, molecular mechanisms underpinning this disadvantage require further enunciation, particularly realize therapeutic opportunities related apoE. This review explores multifaceted roles AD pathogenesis, emphasizing discoveries translational approaches apoE-mediated pathways. These findings underscore potential apoE-based strategies prevent or mitigate genetically at-risk populations.

Language: Английский

Citations

0