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Enhancing the Amyloid-β Anti-Aggregation Properties of Curcumin via Arene-Ruthenium(II) Derivatization

Authors :
Massimiliano Cuccioloni
Valentina Cecarini
Laura Bonfili
Riccardo Pettinari
Alessia Tombesi
Noemi Pagliaricci
Laura Petetta
Mauro Angeletti
Anna Maria Eleuteri
Source :
International Journal of Molecular Sciences, Vol 23, Iss 15, p 8710 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

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.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
23
Issue :
15
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.54c92af4ef2401ba4e6558195c45265
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms23158710