Redox-Dependent Copper Ion Modulation of Amyloid-β (1-42) Aggregation In Vitro.

ABSTRACT: Plaque deposits composed of amyloid-β (Aβ) fibrils are pathological hallmarks of Alzheimer's disease (AD). Although copper ion dyshomeostasis is apparent in AD brains and copper ions are found co-deposited with Aβ peptides in patients' plaques, the molecular effects of copper ion interactions and redox-state dependence on Aβ aggregation remain elusive. By combining biophysical and theoretical approaches, we here show that Cu2+ (oxidized) and Cu+ (reduced) ions have opposite effects on the assembly kinetics of recombinant Aβ(1-42) into amyloid fibrils in vitro. Cu2+ inhibits both the unseeded and seeded aggregation of Aβ(1-42) at pH 8.0. Using mathematical models to fit the kinetic data, we find that Cu2+ prevents fibril elongation. The Cu2+-mediated inhibition of Aβ aggregation shows the l

SUBMITTER: Sasanian N 

PROVIDER: S-EPMC7355640 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature