Title
Oleuropein aglycone stabilizes the monomeric α-synuclein and favours the growth of non-toxic aggregates
Author
Luana Palazzi, Elena Bruzzone, Giovanni Bisello, Manuela Leri, Massimo Stefani, Monica Bucciantini, Patrizia Polverino de Laureto
Year
2018
Journal
Scientific Reports
Abstract
α-synuclein plays a key role in the pathogenesis of Parkinson’s disease (PD); its deposits are found as amyloid fibrils in Lewy bodies and Lewy neurites, the histopathological hallmarks of PD. Amyloid fibrillation is a progressive polymerization path starting from peptide/protein misfolding and proceeding through the transient growth of oligomeric intermediates widely considered as the most toxic species. Consequently, a promising approach of intervention against PD might be preventing α-synuclein build-up, misfolding and aggregation. A possible strategy involves the use of small molecules able to slow down the aggregation process or to alter oligomer conformation favouring the growth of non-pathogenic species. Here, we show that oleuropein aglycone (OleA), the main olive oil polyphenol, exhibits anti-amyloidogenic power in vitro by interacting with, and stabilizing, α-synuclein monomers thus hampering the growth of on-pathway oligomers and favouring the growth of stable and harmless aggregates with no tendency to evolve into other cytotoxic amyloids. We investigated the molecular basis of such interference by both biophysical techniques and limited proteolysis; aggregate morphology was monitored by electron microscopy. We also found that OleA reduces the cytotoxicity of α-synuclein aggregates by hindering their binding to cell membrane components and preventing the resulting oxidative damage to cells.
Full Article
Instrument
FP-6500
Keywords
Fluorescence, Protein structure, Kinetics, Aggregation, Biochemistry