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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
Affiliation:1.School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032 Camerino, MC, Italy;2.School of Pharmacy, University of Camerino, Via Sant’Agostino, 62032 Camerino, MC, Italy;3.School of Science and Technology, University of Camerino, Via Sant’Agostino, 62032 Camerino, MC, Italy
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.
Keywords:Alzheimer’  s disease, amyloid-β  , curcumin, organoruthenium derivative, anti-aggregating molecule
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