Utilisation of the OliveNet™ Library to investigate phenolic compounds using molecular modelling studies in the context of Alzheimer’s disease |
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| Institution: | 1. Epigenomic Medicine, Department of Diabetes, Central Clinical School, Monash University, Prahran, VIC 3004, Australia;2. School of Science, RMIT University, VIC 3001, Australia;3. Department of Microbiology and Immunology (Pathology), The University of Melbourne, Parkville, VIC 3052, Australia;4. Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC 3052, Australia;5. Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3052, Australia;1. Advanced Centre for Bioengineering and Bioinformatics (ACBB), Integral Information and Research Centre (IIRC), Integral University, Lucknow, Uttar Pradesh, 226026, India;2. Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow, Uttar Pradesh, 226026, India;3. Department of EMS, College of Applied Medical Sciences, University of Jazan, Saudi Arabia;1. Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, PR China;2. Laboratory for Marine Drugs and Bioproducts of Pilot National Laboratory for Marine Science and Technology, Qingdao, 266000, PR China;3. Center of Laboratory Medicine, Qilu Hospital of Shandong University (Qingdao), Qingdao, 266100, PR China |
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| Abstract: | Alzheimer’s disease (AD) is a debilitating neurodegenerative disease that affects over 47 million people worldwide, and is the most common form of dementia. There is a vast body of literature demonstrating that the disease is caused by an accumulation of toxic extracellular amyloid-β (Aβ) peptides and intracellular neurofibrillary tangles that consist of hyperphosphorylated tau. Adherence to the Mediterranean diet has been shown to reduce the incidence of AD and the phenolic compounds in extra virgin olive oil, including oleocanthal, have gained a significant amount of attention. A large number of these ligands have been described in the pre-existing literature and 222 of these compounds have been characterised in the OliveNet™ database. In this study, molecular docking was used to screen the 222 phenolic compounds from the OliveNet™ database and assess their ability to bind to various forms of the Aβ and tau proteins. The phenolic ligands were found to be binding strongly to the hairpin-turn of the Aβ1−40 and Aβ1−42 monomers, and binding sites were also identified in the tau fibril protein structures. Luteolin-4′-O-rutinoside, oleuricine A, isorhoifolin, luteolin-7-O-rutinoside, cyanidin-3-O-rutinoside and luteolin-7,4-O-diglucoside were predicted to be novel lead compounds. Molecular dynamics (MD) simulations performed using well-known olive ligands bound to Aβ1−42 oligomers highlighted that future work may examine potential anti-aggregating properties of novel compounds in the OliveNet™ database. This may lead to the development and evaluation of new compounds that may have efficacy against Alzheimer’s disease. |
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| Keywords: | Alzheimer’s disease β-amyloid Amyloid aggregation Tau proteins Phosphorylated tau Olive phenolics |
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