Forskning ved Københavns Universitet - Københavns Universitet

Forside

Trifluoroethanol modulates α-synuclein amyloid-like aggregate formation, stability and dissolution

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

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.

OriginalsprogEngelsk
TidsskriftBiophysical Chemistry
Vol/bind216
Sider (fra-til)23-30
Antal sider8
ISSN0301-4622
DOI
StatusUdgivet - sep. 2016

ID: 168776509