The generation of toxic oligomers during the aggregation of the amyloid-β (Aβ) peptide Aβ42 into amyloid fibrils and plaques has emerged as a central feature of the onset and progression of Alzheimer's disease, but the molecular pathways that control pathological aggregation have proved challenging to identify. Here, we use a combination of kinetic studies, selective radiolabeling experiments, ...

The peptide Boc-Val-Phe-OMe 1 bearing sequence similarity with the central hydrophobic cluster (CHC) of Alzheimer's Aβ(18-19) peptide self-assembles to produce amyloid-like straight unbranched fibrils as examined by atomic force microscopy and Congo red assay. Single crystal X-ray diffraction offers the atomic level structure of the supramolecular parallel β-sheet aggregation and antiparallel s...

Protein misfolding and concomitant aggregation towards amyloid formation is the underlying biochemical commonality among a wide range of human pathologies. Amyloid formation involves the conversion of proteins from their native monomeric states (intrinsically disordered or globular) to well-organized, fibrillar aggregates in a nucleation-dependent manner. Understanding the mechanism of aggregat...