Cellular prion protein targets amyloid-β fibril ends via its C-terminal domain to prevent elongation.

ABSTRACT: Oligomeric forms of the amyloid-β (Aβ) peptide are thought to represent the primary synaptotoxic species underlying the neurodegenerative changes seen in Alzheimer's disease. It has been proposed that the cellular prion protein (PrP^C) functions as a cell-surface receptor, which binds to Aβ oligomers and transduces their toxic effects. However, the molecular details of the PrP^C-Aβ interaction remain uncertain. Here, we investigated the effect of PrP^C on polymerization of Aβ under rigorously controlled conditions in which Aβ converts from a monomeric to a fibrillar state via a series of kinetically defined steps. We demonstrated that PrP^C specifically inhibited elongation of Aβ fibrils, most likely by binding to the ends of growing fibrils. Surpris

SUBMITTER: Bove-Fenderson E 

PROVIDER: S-EPMC5641888 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature