Solid-state NMR analysis of interaction sites of curcumin and 42-residue amyloid β-protein fibrils

Aggregation of 42-residue amyloid beta-protein (A beta 42) plays a pivotal role in the etiology of Alzheimer's disease (AD). Curcumin, the yellow pigment in the rhizome of turmeric, attracts considerable attention as a food component potentially preventing the pathogenesis of AD. This is because curcumin not only inhibits the aggregation of A beta 42 but also binds to its aggregates (fibrils), resulting in disaggregation. However, the mechanism of interaction between curcumin and the A beta 42 fibrils remains unclear. In this study, we analyzed the binding mode of curcumin to the A beta 42 fibrils by solid-state NMR using dipolar-assisted rotational resonance (DARR). To improve the quality of 2D spectra, 2D DARR data were processed with the covariance NMR method, which enabled us to detect weak cross peaks between carbons of curcumin and those of the A beta 42 fibrils. The observed C-13-C-13 cross peaks indicated that curcumin interacts with the 12th and 17-21st residues included in the beta-sheet structure in the A beta 42 fibrils. Interestingly, aromatic carbons adjacent to the methoxy and/or hydroxy groups of curcumin showed clear cross peaks with the A beta 42 fibrils. This suggested that these functional groups of curcumin play an important role in its interaction with the A beta 42 fibrils. (C) 2011 Elsevier Ltd. All rights reserved.