Kumari Rupali, Chaudhary Amit, Mani Ashutosh
Department of Biotechnology, Motilal Nehru National Institute of Technology Allahabad, Prayagraj 211004, India.
Heliyon. 2020 Nov 21;6(11):e05546. doi: 10.1016/j.heliyon.2020.e05546. eCollection 2020 Nov.
Alzheimer's disease is a progressive neurodegenerative disorder. In this disease neurodegeneration occurs due to deposition of aggregated amyloid-beta plaques and neurofibrillary tangles (hyperphosphorylated tau proteins). Present study focuses on interaction of different phytochemicals with presenilin stabilization factor like protein (PSFL). PSFL protein is known to stabilize Presenilin, which is mainly involved in intramembrane hydrolysis of selected type- I membrane proteins, including amyloid-beta precursor protein, and produces amyloid-beta protein. Amyloid-beta are small peptides comprising of 36-43 amino acids, which play a significant role in senile plaques formation in the brains of Alzheimer patients. Virtual screening and docking of phytochemicals with PSFL protein was done to find the potential inhibitor. Based on binding affinity, docked energy and molecular dynamics simulations, three phytochemicals namely Saponin, Casuarictin, and Enoxolone, were identified as potential inhibitors for the target protein.
阿尔茨海默病是一种进行性神经退行性疾病。在这种疾病中，神经退行性变是由于聚集的β-淀粉样蛋白斑块和神经原纤维缠结（过度磷酸化的tau蛋白）沉积所致。目前的研究集中在不同植物化学物质与早老素稳定因子样蛋白（PSFL）的相互作用上。已知PSFL蛋白可稳定早老素，早老素主要参与包括β-淀粉样前体蛋白在内的特定I型膜蛋白的膜内水解，并产生β-淀粉样蛋白。β-淀粉样蛋白是由36-43个氨基酸组成的小肽，在阿尔茨海默病患者大脑中的老年斑形成中起重要作用。对植物化学物质与PSFL蛋白进行虚拟筛选和对接，以寻找潜在的抑制剂。基于结合亲和力、对接能量和分子动力学模拟，确定了三种植物化学物质，即皂苷、苏铁素和甘草次酸，作为目标蛋白的潜在抑制剂。
