title: Ultrasonication-dependent formation and degradation of α-synuclein amyloid fibrils.
abstract: Ultrasonication can be used to break the supersaturation of α-synuclein, a protein associated with Parkinson's disease, at pH7.4 above the critical concentration of fibrillation, thereby inducing the formation of amyloid fibrils. We speculated that ultrasonication could also be used to depolymerize preformed fibrils below the critical concentration. However, extensive ultrasonic irradiation transformed preformed fibrils into amorphous aggregates even above the critical concentration. Exposing preformed fibrils to the hydrophobic air-water interface of cavitation bubbles may have destabilized the fibrils and stabilized amorphous aggregates. Upon extensive ultrasonic irradiation, the accompanying decomposition of chemical structures was suggested when monitored by analytical ultracentrifugation. Amorphous aggregates produced by extensive ultrasonication showed higher cytotoxicity, suggesting that, although ultrasonication might be a useful approach for inactivating amyloid fibrils, potential cytotoxicity of amorphous aggregates should be considered.
authors.affiliation: Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan; Center for Research on Green Sustainable Chemistry, Tottori University, Tottori 680-8552, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yagi
authors.affiliation: Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Mizuno
authors.affiliation: Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
authors.forename: Masatomo
authors.initials: M
authors.lastname: So
authors.affiliation: Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Hirano
authors.affiliation: Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Adachi
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Akazawa-Ogawa
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hagihara
authors.affiliation: Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ikenoue
authors.affiliation: Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Tottori 680-8552, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawata
authors.affiliation: Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan. Electronic address: ygoto@protein.osaka-u.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Goto
mesh_terms: D000682:Amyloid / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000528:radiation effects*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D019220:High-Energy Shock Waves; D016716:PC12 Cells; D066329:Protein Aggregates; D059748:Proteolysis; D011829:Radiation Dosage; D051381:Rats; D013010:Sonication / Q000379:methods*; D051844:alpha-Synuclein / Q000008:administration & dosage / Q000737:chemistry* / Q000528:radiation effects*
chemical_list: D000682:Amyloid; D066329:Protein Aggregates; D051844:alpha-Synuclein
keywords: Amorphous aggregation; Cytotoxicity; Parkinson's disease; Solubility; Supersaturation; Surface denaturation