Medical Laboratory Journal

en Investigating the role of miR-30c in modulating γ-secretase activity: Implications for Alzheimer’s disease ژنتیک انسانی Human Genetics Research Article Research Article <div style="text-align: justify;">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.  </div> Alzheimer Disease, Molecular Docking Simulation, MIRN30C2 microRNA, human, γ-secretase Enzymes 29 33 http://mlj.goums.ac.ir/browse.php?a_code=A-10-1921-1&slc_lang=en&sid=1 Taiebeh Kafshdooz Pourpolsangi 1377317528@iau.ir 100319475328460031695 100319475328460031695 No Department of Biology, Ah.C., Islamic Azad University, Ahar, Iran Rasoul Sharifi rasoulsharifi@iau.ir 100319475328460031696 100319475328460031696 Yes Department of Biology, Ah.C., Islamic Azad University, Ahar, Iran Safar Farajnia farajnia@gmail.com 100319475328460031697 100319475328460031697 No Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Safa Najmi safa.najmi@gmail.com 100319475328460031698 100319475328460031698 No Faculty of Medicine, Tabriz Medical University, Tabriz, Iran