Ali Abuzer, Ganeshpurkar Ankit, Ganeshpurkar Aditya, Dubey Nazneen
Department of Pharmacognosy, College of Pharmacy, Taif University, Taif, Saudi Arabia.
Poona College of Pharmacy, Bharti Vidyapeeth Deemed University, Pune, India.
Int J Med Mushrooms. 2025;27(9):85-92. doi: 10.1615/IntJMedMushrooms.2025059137.
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.
阿尔茨海默病（AD）是神经退行性疾病中的一项重大挑战，其特征是大脑中β淀粉样蛋白（Aβ）斑块和tau蛋白缠结的积累。目前的治疗方法只能缓解症状，无法阻止疾病进展。源自灵芝的灵芝酸A已通过体外和动物模型研究显示出可作为Aβ和tau蛋白聚集的双重抑制剂。本研究旨在利用计算机模拟方法探索灵芝酸A的治疗潜力，以预测其与Aβ和tau蛋白的结合亲和力及相互作用模式。分析包括使用计算模型进行分子对接模拟，以评估灵芝酸A与Aβ和tau蛋白的结合情况。采用了各种工具来预测这些复合物的结合能、相互作用位点（自动对接）和分子动力学（CABSflex 2.0）。灵芝酸A与Aβ和tau蛋白均表现出良好的结合能和相互作用。该化合物通过与参与Aβ聚集和tau蛋白过度磷酸化的关键残基形成稳定复合物，展现出潜在的双重抑制能力。研究结果表明，灵芝酸A有望成为AD中Aβ和tau蛋白聚集的双重抑制剂。通过针对这些关键病理过程，灵芝酸A可能在阻止或减缓疾病进展方面提供治疗益处。要证实这些预测并推动灵芝酸A成为一种可能的AD治疗药物，还需要额外的实验验证，包括体外和体内研究。
