Small-Molecule Inhibitors of Amyloid Beta: Insights from Molecular Dynamics—Part A: Endogenous Compounds and Repurposed Drugs
The amyloid hypothesis is the predominant model of Alzheimer’s disease (AD) pathogenesis, suggesting that amyloid beta (Aβ) peptide is the primary driver of neurotoxicity and a cascade of pathological events in the central nervous system. Aβ aggregation into oligomers and deposits triggers various p...
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MDPI AG
2025-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/18/3/306 |
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| author | Mariyana Atanasova |
| author_facet | Mariyana Atanasova |
| author_sort | Mariyana Atanasova |
| collection | DOAJ |
| description | The amyloid hypothesis is the predominant model of Alzheimer’s disease (AD) pathogenesis, suggesting that amyloid beta (Aβ) peptide is the primary driver of neurotoxicity and a cascade of pathological events in the central nervous system. Aβ aggregation into oligomers and deposits triggers various processes, such as vascular damage, inflammation-induced astrocyte and microglia activation, disrupted neuronal ionic homeostasis, oxidative stress, abnormal kinase and phosphatase activity, tau phosphorylation, neurofibrillary tangle formation, cognitive dysfunction, synaptic loss, cell death, and, ultimately, dementia. Molecular dynamics (MD) is a powerful structure-based drug design (SBDD) approach that aids in understanding the properties, functions, and mechanisms of action or inhibition of biomolecules. As the only method capable of simulating atomic-level internal motions, MD provides unique insights that cannot be obtained through other techniques. Integrating experimental data with MD simulations allows for a more comprehensive understanding of biological processes and molecular interactions. This review summarizes and evaluates MD studies from the past decade on small molecules, including endogenous compounds and repurposed drugs, that inhibit amyloid beta. Furthermore, it outlines key considerations for future MD simulations of amyloid inhibitors, offering a potential framework for studies aimed at elucidating the mechanisms of amyloid beta inhibition by small molecules. |
| format | Article |
| id | doaj-art-b98822c5cd6e4e4b83095ceb5a60a3f0 |
| institution | DOAJ |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-b98822c5cd6e4e4b83095ceb5a60a3f02025-08-20T02:42:28ZengMDPI AGPharmaceuticals1424-82472025-02-0118330610.3390/ph18030306Small-Molecule Inhibitors of Amyloid Beta: Insights from Molecular Dynamics—Part A: Endogenous Compounds and Repurposed DrugsMariyana Atanasova0Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaThe amyloid hypothesis is the predominant model of Alzheimer’s disease (AD) pathogenesis, suggesting that amyloid beta (Aβ) peptide is the primary driver of neurotoxicity and a cascade of pathological events in the central nervous system. Aβ aggregation into oligomers and deposits triggers various processes, such as vascular damage, inflammation-induced astrocyte and microglia activation, disrupted neuronal ionic homeostasis, oxidative stress, abnormal kinase and phosphatase activity, tau phosphorylation, neurofibrillary tangle formation, cognitive dysfunction, synaptic loss, cell death, and, ultimately, dementia. Molecular dynamics (MD) is a powerful structure-based drug design (SBDD) approach that aids in understanding the properties, functions, and mechanisms of action or inhibition of biomolecules. As the only method capable of simulating atomic-level internal motions, MD provides unique insights that cannot be obtained through other techniques. Integrating experimental data with MD simulations allows for a more comprehensive understanding of biological processes and molecular interactions. This review summarizes and evaluates MD studies from the past decade on small molecules, including endogenous compounds and repurposed drugs, that inhibit amyloid beta. Furthermore, it outlines key considerations for future MD simulations of amyloid inhibitors, offering a potential framework for studies aimed at elucidating the mechanisms of amyloid beta inhibition by small molecules.https://www.mdpi.com/1424-8247/18/3/306amyloid betaamyloidosismolecular dynamics (MD)Alzheimer’s disease (AD)amyloid beta inhibitors |
| spellingShingle | Mariyana Atanasova Small-Molecule Inhibitors of Amyloid Beta: Insights from Molecular Dynamics—Part A: Endogenous Compounds and Repurposed Drugs Pharmaceuticals amyloid beta amyloidosis molecular dynamics (MD) Alzheimer’s disease (AD) amyloid beta inhibitors |
| title | Small-Molecule Inhibitors of Amyloid Beta: Insights from Molecular Dynamics—Part A: Endogenous Compounds and Repurposed Drugs |
| title_full | Small-Molecule Inhibitors of Amyloid Beta: Insights from Molecular Dynamics—Part A: Endogenous Compounds and Repurposed Drugs |
| title_fullStr | Small-Molecule Inhibitors of Amyloid Beta: Insights from Molecular Dynamics—Part A: Endogenous Compounds and Repurposed Drugs |
| title_full_unstemmed | Small-Molecule Inhibitors of Amyloid Beta: Insights from Molecular Dynamics—Part A: Endogenous Compounds and Repurposed Drugs |
| title_short | Small-Molecule Inhibitors of Amyloid Beta: Insights from Molecular Dynamics—Part A: Endogenous Compounds and Repurposed Drugs |
| title_sort | small molecule inhibitors of amyloid beta insights from molecular dynamics part a endogenous compounds and repurposed drugs |
| topic | amyloid beta amyloidosis molecular dynamics (MD) Alzheimer’s disease (AD) amyloid beta inhibitors |
| url | https://www.mdpi.com/1424-8247/18/3/306 |
| work_keys_str_mv | AT mariyanaatanasova smallmoleculeinhibitorsofamyloidbetainsightsfrommoleculardynamicspartaendogenouscompoundsandrepurposeddrugs |