(138d) Interactions between ?-Amyloid and ?-Synuclein for Amyloid Co-Assembly | AIChE

(138d) Interactions between ?-Amyloid and ?-Synuclein for Amyloid Co-Assembly


Chau, E. - Presenter, New York University
Candreva, J., New York University
Kim, J. R., New York University
Rice, M., New York University School of Medicine
β-amyloid (Aβ) and α-synuclein (αS) are the primary proteins associated with the pathological hallmarks of neurodegenerative diseases: Aβ in the amyloid plaques of Alzheimer’s disease and αS in the Lewy bodies of Parkinson’s 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 Aβ and αS 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 Aβ and αS 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 Aβ and αS interactions vary depending on their respective aggregation states. We also identify a key Aβ fragment responsible for interaction with αS. Collectively, our data demonstrate aggregation state-specific interactions between αS and Aβ, and offer insight into a molecular basis of synergistic toxic effects between the two polypeptides.