%0 Journal Article
%T Quantifying Co-Oligomer Formation by ¦Á-Synuclein
%J -
%D 2018
%R https://doi.org/10.1021/acsnano.8b03575
%X High Resolution Image Download MS PowerPoint Slide Small oligomers of the protein ¦Á-synuclein (¦ÁS) are highly cytotoxic species associated with Parkinson¡¯s disease (PD). In addition, ¦ÁS can form co-aggregates with its mutational variants and with other proteins such as amyloid-¦Â (A¦Â) and tau, which are implicated in Alzheimer¡¯s disease. The processes of self-oligomerization and co-oligomerization of ¦ÁS are, however, challenging to study quantitatively. Here, we have utilized single-molecule techniques to measure the equilibrium populations of oligomers formed in vitro by mixtures of wild-type ¦ÁS with its mutational variants and with A¦Â40, A¦Â42, and a fragment of tau. Using a statistical mechanical model, we find that co-oligomer formation is generally more favorable than self-oligomer formation at equilibrium. Furthermore, self-oligomers more potently disrupt lipid membranes than do co-oligomers. However, this difference is sometimes outweighed by the greater formation propensity of co-oligomers when multiple proteins coexist. Our results suggest that co-oligomer formation may be important in PD and related neurodegenerative diseases
%U https://pubs.acs.org/doi/10.1021/acsnano.8b03575