ヒラハラ　ユキエ   HIRAHARA YUKIE   平原　幸恵    所属   関西医科大学  基礎看護学領域    職種   教授
論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	査読あり
表題	Keto form of curcumin derivatives strongly binds to Aβ oligomers but not fibrils
掲載誌名	正式名：Biomaterials 略　 称：Biomaterials ISSNコード：01429612
掲載区分	国外
巻・号・頁	270,pp.120686
著者・共著者	Yanagisawa D, Kato T, Taguchi H, Shirai N, Hirao K, Sogabe T, Tomiyama T, Gamo K, Hirahara Y, Kitada M, Tooyama I
発行年月	2021/03
概要	The accumulation of β-amyloid (Aβ) aggregates in the brain occurs early in the progression of Alzheimer's disease (AD), and non-fibrillar soluble Aβ oligomers are particularly neurotoxic. During binding to Aβ fibrils, curcumin, which can exist in an equilibrium state between its keto and enol tautomers, exists predominantly in the enol form, and binding activity of the keto form to Aβ fibrils is much weaker. Here we described the strong binding activity the keto form of curcumin derivative Shiga-Y51 shows for Aβ oligomers and its scant affinity for Aβ fibrils. Furthermore, with imaging mass spectrometry we revealed the blood-brain barrier permeability of Shiga-Y51 and its accumulation in the cerebral cortex and the hippocampus, where Aβ oligomers were mainly localized, in a mouse model of AD. The keto form of curcumin derivatives like Shiga-Y51 could be promising seed compounds to develop imaging probes and therapeutic agents targeting Aβ oligomers in the brain.
DOI	10.1016/j.biomaterials.2021.120686
PMID	33540171