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image of Identification of MicroRNA Drug Targets for Alzheimer's and Diabetes Mellitus Using Network Medicine

Abstract

Introduction

Type 2 diabetes mellitus (T2D) is a known risk factor for developing Alzheimer’s disease (AD). Recent research shows that both diseases share complex and related pathophysiological processes. Network medicine approaches can help to elucidate common dysregulated processes among different diseases, such as AD and T2D. Thus, the aim of this work was to determine differentially expressed genes (DEGs) in AD and T2D and to apply a network medicine approach to identify the microRNAs (miRNAs) involved in the AD-T2D association.

Methods

Gene expression microarray data sets consisting of 384 control samples and 399 samples belonging to AD and T2D disease were analyzed to obtain DEGs shared by both diseases; the miRNAs associated with these DEGs were predicted using a network medicine approach. Finally, potential small molecules targeting these potentially deregulated miRNAs were identified.

Results

AD and T2D shared a subset of 82 downregulated DEGs. These genes were significantly associated ( 0.01) with the ontology terms of chemical synaptic deregulation. DEGs were associated with 12 miRNAs expressed in specific tissues for AD and T2D. Such miRNAs were also primarily associated with the ontology terms related to synaptic deregulation and cancer, and AKT signaling pathways. Steroid anti-inflammatory drugs, antineoplastics, and glucose metabolites were predicted to be potential regulators of the 12 shared miRNAs.

Discussion

The network medicine approach integrating DEGs and miRNAs enabled the identification of shared, potentially deregulated biological processes and pathways underlying the pathophysiology of AD and T2D. These common molecular mechanisms were also linked to drugs currently used in clinical practice, suggesting that this strategy may inform future drug repurposing efforts. Nonetheless, further in-depth biological validation is required to confirm these findings.

Conclusion

Network medicine allowed identifying 12 miRNAs involved in the AD-T2D association, and these could be drug targets for the design of new treatments; however, the identified miRNAs need further experimental confirmation.

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2025-07-14
2025-09-12

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Identification of MicroRNA Drug Targets for Alzheimer's and Diabetes Mellitus Using Network Medicine
Bentham Science Publishers ; https://doi.org/10.2174/0115672050393875250626065205
/content/journals/car/10.2174/0115672050393875250626065205
/content/journals/car/10.2174/0115672050393875250626065205
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  • Article Type:     Research Article
Keywords: metabolic disorder ; Alzheimer's disease ; diabetes mellitus ; drug design ; microRNAs ; Network medicine

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