title: Solid-state NMR analysis of interaction sites of curcumin and 42-residue amyloid β-protein fibrils.
abstract: Aggregation of 42-residue amyloid β-protein (Aβ42) 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 Aβ42 but also binds to its aggregates (fibrils), resulting in disaggregation. However, the mechanism of interaction between curcumin and the Aβ42 fibrils remains unclear. In this study, we analyzed the binding mode of curcumin to the Aβ42 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 Aβ42 fibrils. The observed (13)C-(13)C cross peaks indicated that curcumin interacts with the 12th and 17-21st residues included in the β-sheet structure in the Aβ42 fibrils. Interestingly, aromatic carbons adjacent to the methoxy and/or hydroxy groups of curcumin showed clear cross peaks with the Aβ42 fibrils. This suggested that these functional groups of curcumin play an important role in its interaction with the Aβ42 fibrils.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan. masuda@mail.pharm.tohoku.ac.jp
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Masuda
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukuchi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yatagawa
authors.forename: Masato
authors.initials: M
authors.lastname: Tada
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Takeda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Irie
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Akagi
authors.forename: Youko
authors.initials: Y
authors.lastname: Monobe
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Imazawa
authors.forename: K
authors.initials: K
authors.lastname: Takegoshi
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D020134:Catalytic Domain; D003474:Curcumin / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D003474:Curcumin