title: Optimized Ultrasonic Irradiation Finds Out Ultrastable Aβ1-40Oligomers.
abstract: Oligomer species of amyloid β (Aβ) peptides are intensively investigated because of their relevance to Alzheimer's disease (AD), and a stable oligomer will be a cause of AD. In this article, we investigate the structural stability of two representative Aβ1-40oligomers, which are with and without the β-sheet structure, denoted by β and non-β oligomers, respectively, using optimized ultrasonic irradiation (OUI). Recent studies reveal that OUI significantly accelerates the fibril formation in Aβ1-40monomers; it is capable of transforming any unstable oligomers into fibrils (the dead-end products) in a short time. First, we find that β oligomers can be produced under high-speed stirring agitation; their β-sheet structures are evaluated by the circular-dichroism spectrum measurement, by the immunoassay using the fibril-specific OC antibody, and by the seeding experiment, showing identical characteristics to those formed in previous reports. Second, we form non-β oligomers in a high-concentration NaCl solution and confirm that they include no β-sheet structure, and they are recognized by the oligomer-specific A11 antibody. Furthermore, we confirm the neurotoxicity of the two types of oligomers using the neural tissue derived from mouse embryonic stem cells. We apply the OUI agitation to the β and non-β oligomers. The non-β oligomers are transformed into the fibrils, indicating that they are intermediate species in the fibrillation pathway. However, the β oligomers are surprisingly unaffected by OUI, indicating their high thermodynamic stability. We conclude that the β oligomers should be the independent dead-end products of another pathway, different from the fibrillation pathway.
authors.affiliation: Graduate School of Engineering Science, Osaka University , Toyonaka, Osaka 560-8531, Japan.
authors.forename: Kichitaro
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Institute for Protein Research, Osaka University , Suita, Osaka 565-0871, Japan.
authors.forename: Masatomo
authors.initials: M
authors.lastname: So
authors.affiliation: School of Life Science and Technology, Tokyo Institute of Technology , 4259 B51, Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: School of Life Science and Technology, Tokyo Institute of Technology , 4259 B51, Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan.
authors.forename: Yoh-Ichi
authors.initials: YI
authors.lastname: Tagawa
authors.affiliation: Graduate School of Engineering Science, Osaka University , Toyonaka, Osaka 560-8531, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hirao
authors.affiliation: Institute for Protein Research, Osaka University , Suita, Osaka 565-0871, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Graduate School of Engineering Science, Osaka University , Toyonaka, Osaka 560-8531, Japan.
authors.forename: Hirotsugu
authors.identifier: 0000-0001-9684-4715
authors.initials: H
authors.lastname: Ogi
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D006801:Humans; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D066329:Protein Aggregates / Q000528:radiation effects; D055550:Protein Stability / Q000528:radiation effects*; D051381:Rats; D000069453:Ultrasonic Waves
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D066329:Protein Aggregates; C075222:amyloid beta-protein (1-42)