Dataset Information

Investigating the Neuroprotective Effects of Turmeric Extract: Structural Interactions of ?-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 A?-peptide. When the CYC and curcumin metabolite tetrahydrocurcumin (5, THC) were inserted into an anionic lipid solution, a significant modification of the A? 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-A? interaction, highlighting the importance of a constrained "semi-folded" conformation to interact with A? analogously to the pattern observed in ?-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.

SUBMITTER: Randino R

PROVIDER: S-EPMC5177957 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Investigating the Neuroprotective Effects of Turmeric Extract: Structural Interactions of β-Amyloid Peptide with Single Curcuminoids.

Randino Rosario R Grimaldi Manuela M Persico Marco M De Santis Augusta A Cini Elena E Cabri Walter W Riva Antonella A D'Errico Gerardino G Fattorusso Caterina C D'Ursi Anna Maria AM Rodriquez Manuela M

Scientific reports 20161222

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 s ...[more]

PMID: 28004737

Similar Datasets

Project description:Oxidative stress has been suggested to contribute to neuronal apoptosis associated with Alzheimer's disease (AD). Copper may participate in oxidative stress through redox-cycling between its +2 and +1 oxidation states to generate reactive oxygen species (ROS). In vitro, copper binds to the amyloid-beta peptide of AD, and in vivo, copper is associated with amyloid plaques characteristic of AD. As a result, the AbetaCu(I) complex may be a critical reactant involved in ROS associated with AD etiology. To characterize the AbetaCu(I) complex, we have pursued X-ray absorption (XAS) and electron paramagnetic resonance (EPR) spectroscopy of AbetaCu(II) and AbetaCu(I) (produced by ascorbate reduction of AbetaCu(II)). The AbetaCu(II) complex Cu K-edge XAS spectrum is indicative of a square-planar Cu(II) center with mixed N/O ligation. Multiple scattering analysis of the extended X-ray absorption fine structure (EXAFS) data for AbetaCu(II) indicates that two of the ligands are imidazole groups of histidine ligands, indicating a (N(Im))(2)(N/O)(2) Cu(II) ligation sphere for AbetaCu(II). After reduction of the AbetaCu(II) complex with ascorbate, the edge region decreases in energy by approximately 4 eV. The X-ray absorption near-edge spectrum region of AbetaCu(I) displays an intense pre-edge feature at 8984.1(2) eV. EXAFS data fitting yielded a two-coordinate geometry, with two imidazole ligands coordinated to Cu(I) at 1.877(2) A in a linear geometry. Ascorbate reduction of AbetaCu(II) under inert atmosphere and subsequent air oxidation of AbetaCu(I) to regenerate AbetaCu(II) was monitored by low-temperature EPR spectroscopy. Slow reappearance of the AbetaCu(II) EPR signal indicates that O(2) oxidation of the AbetaCu(I) complex is kinetically sluggish and Abeta damage is occurring following reoxidation of AbetaCu(I) by O(2). Together, these results lead us to hypothesize that Cu(I) is ligated by His13 and His14 in a linear coordination environment in Alphabeta, that Abeta may be playing a neuroprotective role, and that metal-mediated oxidative damage of Abeta occurs over multiple redox cycles.

Dataset Information

Investigating the Neuroprotective Effects of Turmeric Extract: Structural Interactions of ?-Amyloid Peptide with Single Curcuminoids.

Publications

Investigating the Neuroprotective Effects of Turmeric Extract: Structural Interactions of β-Amyloid Peptide with Single Curcuminoids.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets