title: Phenolic compounds prevent amyloid β-protein oligomerization and synaptic dysfunction by site-specific binding.
abstract: Cerebral deposition of amyloid β protein (Aβ) is an invariant feature of Alzheimer disease (AD), and epidemiological evidence suggests that moderate consumption of foods enriched with phenolic compounds reduce the incidence of AD. We reported previously that the phenolic compounds myricetin (Myr) and rosmarinic acid (RA) inhibited Aβ aggregation in vitro and in vivo. To elucidate a mechanistic basis for these results, we analyzed the effects of five phenolic compounds in the Aβ aggregation process and in oligomer-induced synaptic toxicities. We now report that the phenolic compounds blocked Aβ oligomerization, and Myr promoted significant NMR chemical shift changes of monomeric Aβ. Both Myr and RA reduced cellular toxicity and synaptic dysfunction of the Aβ oligomers. These results suggest that Myr and RA may play key roles in blocking the toxicity and early assembly processes associated with Aβ through different binding.
authors.affiliation: Department of Neurology and Neurobiology and Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ono
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Takamura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yoshiike
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhu
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.forename: Xian
authors.initials: X
authors.lastname: Mao
authors.forename: Tokuhei
authors.initials: T
authors.lastname: Ikeda
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Takasaki
authors.forename: Hisao
authors.initials: H
authors.lastname: Nishijo
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takashima
authors.forename: David B
authors.initials: DB
authors.lastname: Teplow
authors.forename: Michael G
authors.initials: MG
authors.lastname: Zagorski
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002934:Cinnamates / Q000494:pharmacology*; D053630:Depsides / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D055503:Protein Multimerization / Q000187:drug effects*; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D000097123:Rosmarinic Acid
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002934:Cinnamates; D053630:Depsides; D005419:Flavonoids; D000097123:Rosmarinic Acid; C040015:myricetin