title: Curcuminoid binds to amyloid-β1-42 oligomer and fibril.
abstract: Studies of Alzheimer's disease (AD) strongly support the hypothesis that amyloid-β (Aβ) deposition in the brain is the initiating event in the progression of AD. Aβ peptides easily form long insoluble amyloid fibrils, which accumulate in deposits known as senile plaques. On the other hand, recent work indicated that soluble Aβ oligomers, rather than monomers or insoluble Aβ fibrils, might be responsible for neuronal and synaptic dysfunction in AD. Curcumin, a low molecular weight yellow-orange pigment derived from the turmeric plant, has shown therapeutic effects in transgenic mouse models of AD. However, it remains unclear whether curcumin interacts directly with the Aβ oligomers. This study investigated any interaction between curcumin and Aβ oligomers such as globulomer and Aβ-derived diffusible ligand (ADDL). Globulomer was observed as a cluster of spherical structures by electron microscopic analysis, and ADDL was also detected as small spherical structures. Fluorescence analysis revealed a significant increase in the fluorescence of curcumin when reacted with both oligomers. Furthermore quartz crystal microbalance analysis showed significant frequency decreases in oligomer-immobilized electrodes following the addition of curcumin. These results strongly suggested that curcumin binds to Aβ oligomers and to Aβ fibrils. The association of curcumin with Aβ oligomers may contribute to the therapeutic effect on AD. Based on these findings, curcumin could provide the basis of a novel concept in AD therapies targeting Aβ oligomers.
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Japan.
authors.forename: Daijiro
authors.initials: D
authors.lastname: Yanagisawa
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Taguchi
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shirai
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirao
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tooyama
mesh_terms: D000682:Amyloid / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000648:ultrastructure; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D052160:Benzothiazoles; D003474:Curcumin / Q000737:chemistry / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D017348:Microscopy, Electron, Scanning Transmission / Q000379:methods; D010446:Peptide Fragments / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding / Q000187:drug effects; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); C009462:thioflavin T; D003474:Curcumin