title: Oleuropein aglycone protects transgenic C. elegans strains expressing Aβ42 by reducing plaque load and motor deficit.
abstract: The presence of amyloid aggregates of the 42 amino acid peptide of amyloid beta (Aβ42) in the brain is the characteristic feature of Alzheimer's disease (AD). Amyloid beta (Aβ 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 Aβ aggregation. Here we evaluated the ability of OLE to interfere with Aβ proteotoxicity in vivo by using the transgenic CL2006 and CL4176 strains of Caenorhabditis elegans, simplified models of AD and of sIBM, which express human Aβ in the cytoplasm of body wall muscle cells. OLE-fed CL2006 worms displayed reduced Aβ plaque deposition, less abundant toxic Aβ 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 Aβ 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 Aβ aggregation skipping the appearance of toxic species, as already shown in vitro for Aβ42.
authors.affiliation: Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. luisa.diomede@marionegri.it
authors.forename: Luisa
authors.initials: L
authors.lastname: Diomede
authors.forename: Stefania
authors.initials: S
authors.lastname: Rigacci
authors.forename: Margherita
authors.initials: M
authors.lastname: Romeo
authors.forename: Massimo
authors.initials: M
authors.lastname: Stefani
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D002107:Caenorhabditis / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D057888:Iridoid Glucosides; D039823:Iridoids; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D011714:Pyrans / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D057888:Iridoid Glucosides; D039823:Iridoids; D010446:Peptide Fragments; D011714:Pyrans; D014665:Vasodilator Agents; C075222:amyloid beta-protein (1-42); C002769:oleuropein