Sticker-and-spacer model for amyloid beta condensation and fibrillation.

ABSTRACT: A major pathogenic hallmark of Alzheimer's disease is the presence of neurotoxic plaques composed of amyloid beta (Aβ) peptides in patients' brains. The pathway of plaque formation remains elusive, though some clues appear to lie in the dominant presence of Aβ_{1 - 42} in these plaques despite Aβ_1-40 making up approximately 90% of the Aβ pool. We hypothesize that this asymmetry is driven by the hydrophobicity of the two extra amino acids that are incorporated in Aβ_1-42. To investigate this hypothesis at the level of single molecules, we have developed a molecular "sticker-and-spacer lattice model" of unfolded Aβ. The model protein has a single sticker that may reversibly dimerise and elongate into semi-flexible linear chains. The growth is hampered by excluded

SUBMITTER: Connor JP 

PROVIDER: S-EPMC9611774 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature