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Updated: Jun 3, 2026
04:22
Biomarker Identification for Gender Specificity of Alzheimer's Disease Based on the Glial Transcriptome Profiles
Published on: May 20, 2024
Integrative Transcriptomic, Network, and Machine Learning Analyses Identify Genistein and Resveratrol-Associated
Murat Isıyel1, Hamid Ceylan2,3, Yeliz Demir4,5
1Faculty of Science, Department of Molecular Biology and Genetics, Atatürk University, Erzurum, Türkiye.
Molecular Neurobiology
|June 2, 2026
Summary
This study identifies four key genes (COX5B, ENO1, HSP90AB1, SDHB) involved in mitochondrial and proteostasis pathways as potential therapeutic targets for Alzheimer's disease (AD). These targets show promise for polyphenol-based treatments.
Area of Science:
- Neuroscience
- Molecular Biology
- Computational Biology
Background:
- Alzheimer's disease (AD) involves complex molecular changes across brain regions.
- Identifying robust therapeutic targets is crucial for AD treatment.
Purpose of the Study:
- To identify pharmacologically relevant molecular targets in Alzheimer's disease using an integrative systems-level approach.
- To investigate the role of mitochondrial bioenergetics and proteostasis in AD pathogenesis.
- To evaluate potential therapeutic strategies involving polyphenols like genistein and resveratrol.
Main Methods:
- Transcriptomic analysis of four AD-related brain regions.
- Protein-protein interaction network analysis to identify hub genes.
- Machine learning (random forest) for validation and feature importance.
- In silico molecular docking to assess polyphenol binding affinities.
Main Results:
- Identified 467 consistently dysregulated genes across all analyzed brain regions.
- Network analysis revealed downregulated hub genes linked to mitochondrial bioenergetics and proteostasis.
- Prioritized COX5B, ENO1, HSP90AB1, and SDHB as key shared targets.
- Machine learning highlighted SDHB, COX5B, and ENO1 as influential contributors.
- Genistein and resveratrol showed favorable binding affinities to the identified targets.
Conclusions:
- A convergent mitochondrial-proteostasis dysfunction axis is implicated in Alzheimer's disease.
- COX5B, ENO1, HSP90AB1, and SDHB represent promising multi-target nodes for AD therapy.
- Polyphenol-based strategies targeting these genes may offer a novel therapeutic avenue for AD.
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