In Silico Investigation of Ganoderic Acid A Targeting Amyloid-Beta and Tau Protein Aggregation in Alzheimer's Disease

Alzheimer's disease (AD) represents a significant challenge in neurodegenerative disorders, characterized by the accumulation of amyloid-beta (Aβ) plaques and tau protein tangles in the brain. Current treatments provide symptomatic relief but do not halt disease progression. ganoderic acid A, derived from Ganoderma lucidum, has shown to act as a dual inhibitor of Aβ and tau protein aggregation through in vitro and animal model studies. This study aims to explore the therapeutic potential of ganoderic acid A using in silico methods to predict its binding affinity and mode of interaction with Aβ and tau proteins. Analysis included molecular docking simulations using computational models to evaluate the binding of ganoderic acid A to Aβ and tau proteins. Various tools were employed to predict the binding energy, interaction sites (Autodock), and MD (CABSflex 2.0) of these complexes. Ganoderic acid A demonstrated favorable binding energies and interactions with both Aβ and tau proteins. The compound exhibited potential dual inhibition capabilities by forming stable complexes with critical residues involved in Aβ aggregation and tau protein hyperphosphorylation. The findings suggest that ganoderic acid A holds promise as a dual inhibitor of Aβ and tau protein aggregation in AD. By targeting these key pathological processes, ganoderic acid A may offer therapeutic benefits in halting or slowing disease progression. Confirming these predictions and advancing ganoderic acid A as a possible AD treatment will require additional experimental validation, including in vitro and in vivo research.