Title : Exploring the role of selenium and selenoproteins in alzheimer’s type disease and tau protein regulation: A molecular docking approach
Abstract:
Introduction: Alzheimer’s disease (AD), the most common form of dementia, currently affects over 55 million people, projected to reach 153 million by 2050.The pathological alteration of tau protein, which plays a central role in the progression of neurodegenerative diseases, including tauopathies.
Material & methods: The serum concentrations of selenium were determined using Atomic Absorption Spectrometry (PinAAcle 900T AA Spectrometer) with the graphite furnace method. Molecular docking was performed to analyze the potential binding mechanisms of selenoprotein and their role in influencing tau protein pathology. Homology models of Microtubule-Associated Protein Tau (PDB ID: 2MZ7) and selenoprotein (PDB ID: 6ELW & 2Q2F) were generated using SWISS-MODEL. The resulting models were assessed for structural alignment using RMSD analysis and visualized with BIOVIA Discovery Studio to interpret the binding interactions effectively.
Results & Discussion: The selenium levels were significantly lower in Alzheimer’s disease (AD) patients (mean=7.8, SD = 2.10) compared to controls (mean=15.466, SD = 1.195), with a t-value of 17.333 (p < 0.0001), suggesting selenium deficiency's potential role in AD pathology. Selenium, as selenoproteins, provides neuroprotection by inhibiting lipid peroxidation, regulating apoptosis, reducing amyloid-beta accumulation, and mitigating tau damage. Selenoproteins' redox center interacts with cysteine, histidine, and arginine, stabilizing enzymatic reactions and neutralizing reactive oxygen species (ROS). Excessive ROS damages cells and exacerbates tau pathology, while selenoprotein P regulates kinases and phosphatases, preserving redox balance. Selenoproteins reduce tau hyperphosphorylation and aggregation, highlighting selenium’s therapeutic potential in Alzheimer’s disease by targeting molecular mechanisms.
Conclusion: Selenium plays a critical role in Alzheimer's disease (AD) pathology through selenoproteins, influencing tau hyperphosphorylation. Selenoprotein P deficiency is linked to AD progression, while selenium supplementation, both inorganic and organic, offers therapeutic potential.
Keyword: Alzheimer’s, Selenium, Docking, Tau, ROS
