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Enhancing the Amyloid-β Anti-Aggregation Properties of Curcumin via Arene-Ruthenium(II) Derivatization
Alzheimer’s disease (AD) is a fatal neurodegenerative disorder associated with severe dementia, progressive cognitive decline, and irreversible memory loss. Although its etiopathogenesis is still unclear, the aggregation of amyloid-β (Aβ) peptides into supramolecular structures and their accumulatio...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369426/ https://www.ncbi.nlm.nih.gov/pubmed/35955845 http://dx.doi.org/10.3390/ijms23158710 |
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author | Cuccioloni, Massimiliano Cecarini, Valentina Bonfili, Laura Pettinari, Riccardo Tombesi, Alessia Pagliaricci, Noemi Petetta, Laura Angeletti, Mauro Eleuteri, Anna Maria |
author_facet | Cuccioloni, Massimiliano Cecarini, Valentina Bonfili, Laura Pettinari, Riccardo Tombesi, Alessia Pagliaricci, Noemi Petetta, Laura Angeletti, Mauro Eleuteri, Anna Maria |
author_sort | Cuccioloni, Massimiliano |
collection | PubMed |
description | Alzheimer’s disease (AD) is a fatal neurodegenerative disorder associated with severe dementia, progressive cognitive decline, and irreversible memory loss. Although its etiopathogenesis is still unclear, the aggregation of amyloid-β (Aβ) peptides into supramolecular structures and their accumulation in the central nervous system play a critical role in the onset and progression of the disease. On such a premise, the inhibition of the early stages of Aβ aggregation is a potential prevention strategy for the treatment of AD. Since several natural occurring compounds, as well as metal-based molecules, showed promising inhibitory activities toward Aβ aggregation, we herein characterized the interaction of an organoruthenium derivative of curcumin with Aβ(1–40) and Aβ(1–42) peptides, and we evaluated its ability to inhibit the oligomerization/fibrillogenesis processes by combining in silico and in vitro methods. In general, besides being less toxic to neuronal cells, the derivative preserved the amyloid binding ability of the parent compound in terms of equilibrium dissociation constants but (most notably) was more effective both in retarding the formation and limiting the size of amyloid aggregates by virtue of a higher hindering effect on the amyloid–amyloid elongation surface. Additionally, the complex protected neuronal cells from amyloid toxicity. |
format | Online Article Text |
id | pubmed-9369426 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93694262022-08-12 Enhancing the Amyloid-β Anti-Aggregation Properties of Curcumin via Arene-Ruthenium(II) Derivatization Cuccioloni, Massimiliano Cecarini, Valentina Bonfili, Laura Pettinari, Riccardo Tombesi, Alessia Pagliaricci, Noemi Petetta, Laura Angeletti, Mauro Eleuteri, Anna Maria Int J Mol Sci Article Alzheimer’s disease (AD) is a fatal neurodegenerative disorder associated with severe dementia, progressive cognitive decline, and irreversible memory loss. Although its etiopathogenesis is still unclear, the aggregation of amyloid-β (Aβ) peptides into supramolecular structures and their accumulation in the central nervous system play a critical role in the onset and progression of the disease. On such a premise, the inhibition of the early stages of Aβ aggregation is a potential prevention strategy for the treatment of AD. Since several natural occurring compounds, as well as metal-based molecules, showed promising inhibitory activities toward Aβ aggregation, we herein characterized the interaction of an organoruthenium derivative of curcumin with Aβ(1–40) and Aβ(1–42) peptides, and we evaluated its ability to inhibit the oligomerization/fibrillogenesis processes by combining in silico and in vitro methods. In general, besides being less toxic to neuronal cells, the derivative preserved the amyloid binding ability of the parent compound in terms of equilibrium dissociation constants but (most notably) was more effective both in retarding the formation and limiting the size of amyloid aggregates by virtue of a higher hindering effect on the amyloid–amyloid elongation surface. Additionally, the complex protected neuronal cells from amyloid toxicity. MDPI 2022-08-05 /pmc/articles/PMC9369426/ /pubmed/35955845 http://dx.doi.org/10.3390/ijms23158710 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cuccioloni, Massimiliano Cecarini, Valentina Bonfili, Laura Pettinari, Riccardo Tombesi, Alessia Pagliaricci, Noemi Petetta, Laura Angeletti, Mauro Eleuteri, Anna Maria Enhancing the Amyloid-β Anti-Aggregation Properties of Curcumin via Arene-Ruthenium(II) Derivatization |
title | Enhancing the Amyloid-β Anti-Aggregation Properties of Curcumin via Arene-Ruthenium(II) Derivatization |
title_full | Enhancing the Amyloid-β Anti-Aggregation Properties of Curcumin via Arene-Ruthenium(II) Derivatization |
title_fullStr | Enhancing the Amyloid-β Anti-Aggregation Properties of Curcumin via Arene-Ruthenium(II) Derivatization |
title_full_unstemmed | Enhancing the Amyloid-β Anti-Aggregation Properties of Curcumin via Arene-Ruthenium(II) Derivatization |
title_short | Enhancing the Amyloid-β Anti-Aggregation Properties of Curcumin via Arene-Ruthenium(II) Derivatization |
title_sort | enhancing the amyloid-β anti-aggregation properties of curcumin via arene-ruthenium(ii) derivatization |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369426/ https://www.ncbi.nlm.nih.gov/pubmed/35955845 http://dx.doi.org/10.3390/ijms23158710 |
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