Insight into the molecular mechanism underlying the inhibition of α-synuclein aggregation by hydroxytyrosol.

摘要: Abstract Parkinson’s disease (PD) is the second most prevalent neurodegenerative in elderly people. To date, drugs able to reverse are not available; gold standard levodopa that only relieves clinical symptoms, yet with severe side effects after prolonged administration. Many efforts underway find alternative targets for PD prevention or treatment, promising being α-synuclein (Syn). Recently, we reported oleuropein aglycone (OleA) interferes amyloid aggregation of Syn both stabilizing its monomeric state and inducing formation harmless, off-pathway oligomers. This study focused at describing interaction between hydroxytyrosol (HT), phenolic moiety main metabolite OleA, interferences by using biophysical biological techniques. Our results show HT dose-dependently inhibits covalent non-covalent binding mediate HT-Syn interaction. does modify natively unfolded structure Syn, rather, it stabilizes specific regions molecule leading inhibition protein fibrillation. Cellular assays showed reduces toxicity aggregates. Moreover, aggregates cell membrane, an important factor prion-like properties on-pathway oligomers, was reduced cells exposed grown presence HT.