TY - JOUR
T1 - Trifluoroethanol modulates α-synuclein amyloid-like aggregate formation, stability and dissolution
AU - Di Carlo, Maria Giovanna
AU - Vetri, Valeria
AU - Buscarino, Gianpiero
AU - Leone, Maurizio
AU - Vestergaard, Bente
AU - Foderà, Vito
N1 - Copyright © 2016 Elsevier B.V. All rights reserved.
PY - 2016/9
Y1 - 2016/9
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1016/j.bpc.2016.06.003
DO - 10.1016/j.bpc.2016.06.003
M3 - Journal article
C2 - 27372900
VL - 216
SP - 23
EP - 30
JO - Biophysical Chemistry
JF - Biophysical Chemistry
SN - 0301-4622
ER -