Publication Date
Winter 2026
Keywords
Alzheimer's, Tau protein
Abstract
Abstract: Alzheimer's Disease (AD) is characterized as "Type 3 Diabetes," where metabolic dysfunction drives Tau protein aggregation. This study uses in silico docking to compare the structural efficacy of three drug classes (Glucose, Lipid, and Cardio-Metabolic) against the Tau paired helical filament. 60 FDA-approved modulators were docked using CB-Dock2. Performance was tiered by Vina score thresholds: Elite (< -8.0 kcal/mol), Moderate (-6.0 to -7.9 kcal/mol), and Weak (> -6.0 kcal/mol). Cardio-Metabolic agents outperformed typical metabolic treatments. Digoxin resulted as the most "Ente' candidate (-9.0 kcal/mon. signincantiv surpassing the standard glucose regulator Mettormin (-4.5 kcal/mon. High-atmity binders also included Fluvastan (-8.2 kcalmon and telmisartan -8.2 kcal/mon. Mechanistcalv. Digoxin's olanar nucleus facintates hydrohobic stacking against the Tau topology, while Metformin's small hydrophilic structure lacks stable occupancy. Applying the "1.4 kcal/mol rule," Digoxin exhibits about 1000-fold higher binding potential than Metformin. These findings validate cardio-metabolic are more successful for neuroprotective drug repurposing rather than simple insulin-sensitizing agents. Future validation will utilize in vivo clinical trials.
Recommended Citation
Chitrapu, Maanya; Vora, Juhi; and Gill Dhillon, Navi, "In Silico Repurposing of FDA-Approved Pleiotropic Metabolic Modulators for Alzheimer's Tau Protein" (2026). Bioinformatics. 16.
https://nsuworks.nova.edu/bioinformatics/16
COinS
This Research has been presented
Undergraduate Student Symposium 2026, Davie FL