(138d) Interactions between ?-Amyloid and ?-Synuclein for Amyloid Co-Assembly
AIChE Annual Meeting
Monday, November 11, 2019 - 1:24pm to 1:42pm
Î²-amyloid (AÎ²) and Î±-synuclein (Î±S) are the primary proteins associated with the pathological hallmarks of neurodegenerative diseases: AÎ² in the amyloid plaques of Alzheimerâs disease and Î±S in the Lewy bodies of Parkinsonâs disease. Both of these amyloid polypeptides follow similar pathways in their aggregation, starting with their monomer subunits, then soluble toxic oligomeric assemblies, and finally insoluble fibrils. Although AÎ² and Î±S affect different regions of the brain and are separated at the cellular level, there is evidence of their eventual interaction in the pathology of both disorders. The interactions of AÎ² and Î±S at various stages of their aggregation pathways could reveal mechanisms and therapeutic targets for the prevention and cure of these neurodegenerative diseases. In this study, we comprehensively examined the interactions and their molecular manifestations using an array of characterization tools. We show that outcomes of AÎ² and Î±S interactions vary depending on their respective aggregation states. We also identify a key AÎ² fragment responsible for interaction with Î±S. Collectively, our data demonstrate aggregation state-specific interactions between Î±S and AÎ², and offer insight into a molecular basis of synergistic toxic effects between the two polypeptides.