Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2012 Sep 28;287(40):33104-8. Epub 2012 Aug 22.

Soluble prion protein inhibits amyloid-β (Aβ) fibrillization and toxicity.

Author information

1
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, USA.

Abstract

The pathogenesis of Alzheimer disease appears to be strongly linked to the aggregation of amyloid-β (Aβ) peptide and, especially, formation of soluble Aβ1-42 oligomers. It was recently demonstrated that the cellular prion protein, PrP(C), binds with high affinity to these oligomers, acting as a putative receptor that mediates at least some of their neurotoxic effects. Here we show that the soluble (i.e. glycophosphatidylinositol anchor-free) prion protein and its N-terminal fragment have a strong effect on the aggregation pathway of Aβ1-42, inhibiting its assembly into amyloid fibrils. Furthermore, the prion protein prevents formation of spherical oligomers that normally occur during Aβ fibrillogenesis, acting as a potent inhibitor of Aβ1-42 toxicity as assessed in experiments with neuronal cell culture. These findings may provide a molecular level foundation to explain the reported protective action of the physiologically released N-terminal N1 fragment of PrP(C) against Aβ neurotoxicity. They also suggest a novel approach to pharmacological intervention in Alzheimer disease.

PMID:
22915585
PMCID:
PMC3460415
DOI:
10.1074/jbc.C112.400614
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center