Oleuropein aglycone protects transgenic C. elegans strains expressing A?42 by reducing plaque load and motor deficit.

ABSTRACT: The presence of amyloid aggregates of the 42 amino acid peptide of amyloid beta (A?42) in the brain is the characteristic feature of Alzheimer's disease (AD). Amyloid beta (A? deposition is also found in muscle fibers of individuals affected by inclusion body myositis (sIBM), a rare muscular degenerative disease affecting people over 50. Both conditions are presently lacking an effective therapeutic treatment. There is increasing evidence to suggest that natural polyphenols may prevent the formation of toxic amyloid aggregates; this applies also to oleuropein aglycone (OLE), the most abundant polyphenol in extra virgin olive oil, previously shown to hinder amylin and A? aggregation. Here we evaluated the ability of OLE to interfere with A? proteotoxicity in vivo by using the transgenic CL2006 and CL4176 strains of Caenorhabditis elegans, simplified models of AD and of sIBM, which express human A? in the cytoplasm of body wall muscle cells. OLE-fed CL2006 worms displayed reduced A? plaque deposition, less abundant toxic A? oligomers, remarkably decreased paralysis and increased lifespan with respect to untreated animals. A protective effect was also observed in CL4176 worms but only when OLE was administered before the induction of the A? transgene expression. These effects were specific, dose-related, and not mediated by the known polyphenolic anti-oxidant activity, suggesting that, in this model organism, OLE interferes with the A? aggregation skipping the appearance of toxic species, as already shown in vitro for A?42.

SUBMITTER: Diomede L 

PROVIDER: S-EPMC3592812 | biostudies-other | 2013

REPOSITORIES: biostudies-other