title: Trifluoroethanol modulates α-synuclein amyloid-like aggregate formation, stability and dissolution.
abstract: The conversion of proteins into amyloid fibrils and other amyloid-like aggregates is closely connected to the onset of a series of age-related pathologies. Upon changes in environmental conditions, amyloid-like aggregates may also undergo disassembly into oligomeric aggregates, the latter being recognized as key effectors in toxicity. This indicates new possible routes for in vivo accumulation of toxic species. In the light of the recognized implication of α-Synuclein (αSN) in Parkinson's disease, we present an experimental study on supramolecular assembly of αSN with a focus on stability and disassembly paths of such supramolecular aggregate species. Using spectroscopic techniques, two-photon microscopy, small-angle X-ray scattering and atomic force microscopy, we report evidences on how the stability of αSN amyloid-like aggregates can be altered by changing solution conditions. We show that amyloid-like aggregate formation can be induced at high temperature in the presence of trifluoroethanol (TFE). Moreover, sudden disassembly or further structural reorganisation toward higher hierarchical species can be induced by varying TFE concentration. Our results may contribute in deciphering fundamental mechanisms and interactions underlying supramolecular clustering/dissolution of αSN oligomers in cells.
authors.affiliation: Dipartimento di Fisica e Chimica, Università degli Studi di Palermo, Viale delle Scienze, Edificio 18, 90128 Palermo, Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Di Carlo
authors.affiliation: Dipartimento di Fisica e Chimica, Università degli Studi di Palermo, Viale delle Scienze, Edificio 18, 90128 Palermo, Italy; Advanced Technologies Network Center, Università degli Studi di Palermo, Palermo, Italy. Electronic address: valeria.vetri@unipa.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Vetri
authors.affiliation: Dipartimento di Fisica e Chimica, Università degli Studi di Palermo, Viale delle Scienze, Edificio 18, 90128 Palermo, Italy.
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Buscarino
authors.affiliation: Dipartimento di Fisica e Chimica, Università degli Studi di Palermo, Viale delle Scienze, Edificio 18, 90128 Palermo, Italy; Advanced Technologies Network Center, Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Leone
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Vestergaard
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark; Section for Biologics, Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. Electronic address: vito.fodera@sund.ku.dk.
authors.forename: Vito
authors.initials: V
authors.lastname: Foderà
mesh_terms: D000682:Amyloid / Q000737:chemistry; D006801:Humans; D066329:Protein Aggregates / Q000187:drug effects*; D055550:Protein Stability; D013057:Spectrum Analysis; D013696:Temperature; D014270:Trifluoroethanol / Q000494:pharmacology*; D051844:alpha-Synuclein / Q000737:chemistry* / Q000187:drug effects
chemical_list: D000682:Amyloid; D066329:Protein Aggregates; D051844:alpha-Synuclein; D014270:Trifluoroethanol