title: Attenuation of the aggregation and neurotoxicity of amyloid-β peptides by catalytic photooxygenation.
abstract: Alzheimer's disease (AD), a progressive severe neurodegenerative disorder, is currently incurable, despite intensive efforts worldwide. Herein, we demonstrate that catalytic oxygenation of amyloid-β peptides (Aβ) might be an effective approach to treat AD. Aβ1-42 was oxygenated under physiologically-relevant conditions (pH 7.4, 37 °C) using a riboflavin catalyst and visible light irradiation, with modifications at the Tyr(10) , His(13) , His(14) , and Met(35) residues. The oxygenated Aβ1-42 exhibited considerably lower aggregation potency and neurotoxicity compared with native Aβ. Photooxygenation of Aβ can be performed even in the presence of cells, by using a selective flavin catalyst attached to an Aβ-binding peptide; the Aβ cytotoxicity was attenuated in this case as well. Furthermore, oxygenated Aβ1-42 inhibited the aggregation and cytotoxicity of native Aβ.
authors: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan); Japan Science and Technology Agency (JST), ERATO, Kanai Life Science Catalysis Project, Bunkyo-ku, Tokyo 113-0033 (Japan).
authors: Atsuhiko
authors: A
authors: Taniguchi
authors: Daisuke
authors: D
authors: Sasaki
authors: Azusa
authors: A
authors: Shiohara
authors: Takeshi
authors: T
authors: Iwatsubo
authors: Taisuke
authors: T
authors: Tomita
authors: Youhei
authors: Y
authors: Sohma
authors: Motomu
authors: M
authors: Kanai
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D002384:Catalysis; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D008027:Light; D008969:Molecular Sequence Data; D010100:Oxygen / Q000737:chemistry*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D012256:Riboflavin / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D010100:Oxygen; D012256:Riboflavin
keywords: Alzheimer’s disease; aggregation; amyloid-beta peptides; oxygenation