title: Investigating the Neuroprotective Effects of Turmeric Extract: Structural Interactions of β-Amyloid Peptide with Single Curcuminoids.
abstract: A broad biophysical analysis was performed to investigate the molecular basis of the neuroprotective action of Curcuma longa extracts in Alzheimer's disease. By combining circular dichroism and electron paramagnetic resonance experiments with molecular modeling calculations, the minor components of Curcuma longa extracts, such as demethoxycurcumin (2, DMC), bisdemethoxycurcumin (3, BDMC) and cyclocurcumin (4, CYC), were analyzed in a membrane environment mimicking the phospholipid bilayer. Our study provides the first evidence on the relative role of single curcuminoids interacting with Aβ-peptide. When the CYC and curcumin metabolite tetrahydrocurcumin (5, THC) were inserted into an anionic lipid solution, a significant modification of the Aβ CD curves was detected. These data were implemented by EPR experiments, demonstrating that CYC reaches the inner part of the bilayer, while the other curcuminoids are localized close to the membrane interface. Computational studies provided a model for the curcuminoid-Aβ interaction, highlighting the importance of a constrained "semi-folded" conformation to interact with Aβ analogously to the pattern observed in α-helical coiled-coil peptide structures. This combined approach led to a better understanding of the intriguing in vitro and in vivo activity of curcuminoids as anti-Alzheimer agents, paving a new path for the rational design of optimized druggable analogues.
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084-Fisciano-Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Randino
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084-Fisciano-Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Grimaldi
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano, 49, 80131-Naples-Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Persico
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", Via Cinthia, 80126-Naples-Italy.
authors.forename: Augusta
authors.initials: A
authors.lastname: De Santis
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro, 2, 53100-Siena-Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Cini
authors.affiliation: R&D Department, Indena, Viale Ortles, 12, 20139-Milan-Italy.|Innovation &Development Fresenius-Kabi, Piazza Maestri del Lavoro, 7, 20063-Cernusco sul Naviglio Milan-Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Cabri
authors.affiliation: R&D Department, Indena, Viale Ortles, 12, 20139-Milan-Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Riva
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", Via Cinthia, 80126-Naples-Italy.
authors.forename: Gerardino
authors.initials: G
authors.lastname: D'Errico
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano, 49, 80131-Naples-Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Fattorusso
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084-Fisciano-Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: D'Ursi
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084-Fisciano-Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Rodriquez
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D003198:Computer Simulation; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000031:analogs & derivatives / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010936:Plant Extracts; C074636:amyloid beta-protein (25-35); D003474:Curcumin