(De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants

Parkinson's disease (PD) is the second most common neurodegenerative disorder. An important hallmark of PD involves the pathological aggregation of proteins in structures known as Lewy bodies. The major component of these proteinaceous inclusions is alpha (alpha)-synuclein. In different conditions, alpha-synuclein can assume conformations rich in either alpha-helix or beta-sheets. The mechanisms of alpha-synuclein misfolding, aggregation, and fibrillation remain unknown, but it is thought that beta-sheet conformation of alpha-synuclein is responsible for its associated toxic mechanisms. To gain fundamental insights into the process of alpha-synuclein misfolding and aggregation, the secondary structure of this protein in the presence of charged and non-charged surfactant solutions was characterized. The selected surfactants were (anionic) sodium dodecyl sulphate (SDS), (cationic) cetyltrimethylammonium chloride (CTAC), and (uncharged) octyl beta-D-glucopyranoside (OG). The effect of surfactants in alpha-synuclein misfolding was assessed by ultra-structural analyses, in vitro aggregation assays, and secondary structure analyses. The alpha-synuclein aggregation in the presence of negatively charged SDS suggests that SDS-monomer complexes stimulate the aggregation process. A reduction in the electrostatic repulsion between N- and C-terminal and in the hydrophobic interactions between the NAC (non-amyloid beta component) region and the C-terminal seems to be important to undergo aggregation. Fourier transform infrared spectroscopy (FTIR) measurements show that beta-sheet structures comprise the assembly of the fibrils.

Automated summary

Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by the pathological aggregation of alpha-synuclein leading to Lewy bodies formation. Research indicates that the beta-sheet conformation of alpha-synuclein in the presence of the anionic surfactant SDS stimulates its aggregation process.