Amyloid Fibril Formation of Arctic Amyloid-β 1-42 Peptide is Efficiently Inhibited by the BRICHOS Domain.

ABSTRACT: Amyloid-β peptide (Aβ) aggregation is one of the hallmarks of Alzheimer's disease (AD). Mutations in Aβ are associated with early onset familial AD, and the Arctic mutant E22G (Aβ^arc) is an extremely aggregation-prone variant. Here, we show that BRICHOS, a natural anti-amyloid chaperone domain, from Bri2 efficiently inhibits aggregation of Aβ^arc by mainly interfering with secondary nucleation. This is qualitatively different from the microscopic inhibition mechanism for the wild-type Aβ, against which Bri2 BRICHOS has a major effect on both secondary nucleation and fibril end elongation. The monomeric Aβ42^arc peptide aggregates into amyloid fibrils significantly faster than wild-type Aβ (Aβ42^wt), as monitored by thioflavin T (ThT) binding, but th

SUBMITTER: Zhong X 

PROVIDER: S-EPMC9396614 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature