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Investigating the role of miR-30c in modulating γ-secretase activity: Implications for Alzheimer’s disease
Taiebeh Kafshdooz Pourpolsangi1 , Rasoul Sharifi2 , Safar Farajnia3 , Safa Najmi4
1- Department of Biology, Ah.C., Islamic Azad University, Ahar, Iran
2- Department of Biology, Ah.C., Islamic Azad University, Ahar, Iran , rasoulsharifi@iau.ir
3- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4- Faculty of Medicine, Tabriz Medical University, Tabriz, Iran
Abstract:   (384 Views)
Background: Alzheimer’s disease (AD), the most common form of dementia, affects millions of people worldwide. Clinical trials using anti-Aβ antibodies demonstrate that amyloid plaque removal in early-stage AD can slow disease progression. Along with β-secretase, γ-secretase plays a role in cleaving amyloid precursor protein (APP). The aim of this study was to use computational docking to identify molecules that can activate γ-secretase.
Methods: Initially, the targets of hsa-miR-30c-5p were assessed using the TargetScanHuman server. The structure of γ-secretase was prepared in Chimera by removing non-standard residues and water molecules. Adjacent amino acids to the cholesterol ligand were then identified using PyMOL. The 3D structure and SMILES notation for cholesterol were obtained from PubChem. Docking results in pdbqt format were analyzed using Discovery Studio, LigPlus+, and PDBsum, with LigPlus+ focusing on protein subunit interactions.
Results: The TargetScanHuman server indicated that γ-secretase is a target of hsa-miR-30c-5p. Drug-like properties (Solubility, tumorigenicity, LogP, toxicity) of compounds were predicted using tools such as SwissTargetPrediction, PASS-Way2Drug, and SwissADME, following Lipinski’s Rule of Five. Amino acids Trp227, Leu192, Arg186, Leu199, Leu203, Leu206, Tyr155, Leu215, Phe162, Ser223, and Ile230, located on the γ-secretase C subunit, were analyzed for interactions using LigPlot after AutoDock Vina docking and Chimera visualization.
Conclusion: These in silico findings suggest cholesterin acetate as a potential activator of γ-secretase; further experimental validation is warranted.
 
Keywords: Alzheimer Disease, Molecular Docking Simulation, MIRN30C2 microRNA, human, γ-secretase Enzymes
Full-Text [PDF 442 kb]   (149 Downloads)    
Research Article: Research Article | Subject: Human Genetics
Received: 2025/04/15 | Accepted: 2025/08/10
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