title: The binding of resveratrol to monomer and fibril amyloid beta.
abstract: As currently understood, Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is driven by the aggregation of amyloid beta (Aβ) protein. It has been shown that resveratrol (RES) may attenuate amyloid β peptide-induced toxicity, promote Aβ clearance and reduce senile plaques. However, it remains to be determined whether RES could interact directly with Aβ. The aim of the present study was to examine the direct binding of RES to monomer and fibril Aβ. Using surface plasmon resonance (SPR) and proton nuclear magnetic resonance ((1)H NMR), our results identified the direct binding of RES to Aβ. The ability of RES to bind to both fibril and monomer Aβ(1-40 and 1-42) was further analyzed by SPR. The binding response of RES to fAβ(1-42) was higher than that to monomer Aβ(1-42), whereas the binding response of RES to fAβ(1-40) was lower than that to monomer Aβ(1-40). The K(D) of RES for fibril Aβ(1-40 or 1-42) was higher than that for the corresponding monomer Aβ. Compared to the control compound Congo red (CR), the binding responses of RES to monomer Aβ(1-42) and Aβ(1-40) were stronger, but binding to fibril Aβ(1-42) was weaker, and the K(D)s of RES with both monomer and fibril Aβ(1-40) and Aβ(1-42) were higher than that of CR. When Aβ(1-40 or 1-42) was co-incubated with RES (50μM), the thioflavin T fluorescence of the mixture was weakened, and the number and length of amyloid fibrils were decreased. Furthermore, the results of staining in consecutive brain slices from AD patients showed that RES (10(-4)M) could stain senile plaques. These results indicated that RES could bind directly to Aβ in different states, which may provide new insight into the protective properties of RES against AD.
authors.affiliation: School of Life Science, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Jin-Fang
authors.initials: JF
authors.lastname: Ge
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Qiao
authors.forename: Cong-Cong
authors.initials: CC
authors.lastname: Qi
authors.forename: Chen-Wei
authors.initials: CW
authors.lastname: Wang
authors.forename: Jiang-Ning
authors.initials: JN
authors.lastname: Zhou
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D011485:Protein Binding; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D016229:Amyloid beta-Peptides; D013267:Stilbenes; D000077185:Resveratrol