Biological and Computational Evaluation of Resveratrol Inhibitors against Alzheimer's Disease
Open accessAbstract
It has been reported that beta amyloid induces production of radical oxygen species and oxidative stress in neuronal cells, which in turn upregulates β-secretase (BACE-1) expression and beta amyloid levels, thereby propagating oxidative stress and increasing neuronal injury. A series of resveratrol derivatives, known to be inhibitors of oxidative stress-induced neuronal cell death (oxytosis) were biologically evaluated against BACE-1 using homogeneous time-resolved fluorescence (TRF) assay. Correlation between oxytosis inhibitory and BACE-1 inhibitory activity of resveratrol derivatives was statistically significant, supporting the notion that BACE-1 may act as pivotal mediator of neuronal cell oxytosis. Four of the biologically evaluated resveratrol analogs demonstrated considerably higher activity than resveratrol in either assay. The discovery of some "hits" led us to initiate detailed docking studies associated with Molecular Dynamics in order to provide a plausible explanation for the experimental results and understand their molecular basis of action.
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Resveratrol affects Aβ production by inhibiting β-secretase activity.
“resveratrol has been demonstrated to affect the Aβ production by inhibiting the activity of β-secretase (Choi et al., 2011; Koukoulitsa et al., 2016)”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Koukoulitsa et al., 2016
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- Authors
- Koukoulitsa, C., Villalonga-Barber, C., Csonka, R., Alexi, X., Leonis, G., Dellis, D., Hamelink, E., Belda, O., Steele, B. R., Micha-Screttas, M., Alexis, M. N., Papadopoulos, M. G., & Mavromoustakos, T.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- National Hellenic Research Foundation (GR)
- Institute of Accelerating Systems and Applications (GR)
- Medivir (Sweden) (SE)
- Corresponding author
- Koukoulitsa, Catherine
- Mavromoustakos, Thomas
- Venue
- Journal of Enzyme Inhibition and Medicinal Chemistry
- Publisher
- Informa UK Limited
- Published
- 2015-07-06
- Volume
- 31
- Issue
- 1
- Pages
- 67-77
- ISSN
- 1475-6366 (ISSN-L)
- 1475-6374
- OpenAlex
- W1884115466
- Cited by
- 37
- References
- 69
- Citations by year
- 2025: 3 · 2023: 2 · 2022: 6 · 2021: 8 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 5 · 2016: 3
- FWCI
- 2.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Enzyme Inhibition and Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Sussex Research Online (University of Sussex) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- National Hellenic Research Foundation Helios Repository (National Hellenic Research Foundation) (submittedVersion)
- Funders
- European Commission
- Università degli Studi di Perugia
- Serbian Academy of Sciences and Arts
- European Social Fund
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- resveratrol derivatives, Alzheimer's disease, amyloid-beta, BACE1, beta-secretase inhibition, oxytosis, oxidative stress, neuronal cell death, resveratrol analogues, molecular docking, molecular dynamics simulation
- MeSH terms
- Resveratrol, Alzheimer Disease, Animals, Cell Line, Dose-Response Relationship, Drug, Neurons, Stilbenes, Structure-Activity Relationship, Molecular Structure, Aspartic Acid Endopeptidases, Cell Death, Oxidative Stress, Mice, Amyloid Precursor Protein Secretases, Molecular Dynamics Simulation
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