Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Cuccioloni, Massimiliano, Cecarini, Valentina, Bonfili, Laura, Pettinari, Riccardo, Tombesi, Alessia, Pagliaricci, Noemi, Petetta, Laura, Angeletti, Mauro, Eleuteri, Anna Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784766454623633408
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
work_keys_str_mv AT cucciolonimassimiliano enhancingtheamyloidbantiaggregationpropertiesofcurcuminviaarenerutheniumiiderivatization
AT cecarinivalentina enhancingtheamyloidbantiaggregationpropertiesofcurcuminviaarenerutheniumiiderivatization
AT bonfililaura enhancingtheamyloidbantiaggregationpropertiesofcurcuminviaarenerutheniumiiderivatization
AT pettinaririccardo enhancingtheamyloidbantiaggregationpropertiesofcurcuminviaarenerutheniumiiderivatization
AT tombesialessia enhancingtheamyloidbantiaggregationpropertiesofcurcuminviaarenerutheniumiiderivatization
AT pagliariccinoemi enhancingtheamyloidbantiaggregationpropertiesofcurcuminviaarenerutheniumiiderivatization
AT petettalaura enhancingtheamyloidbantiaggregationpropertiesofcurcuminviaarenerutheniumiiderivatization
AT angelettimauro enhancingtheamyloidbantiaggregationpropertiesofcurcuminviaarenerutheniumiiderivatization
AT eleuteriannamaria enhancingtheamyloidbantiaggregationpropertiesofcurcuminviaarenerutheniumiiderivatization