Oleuropein aglycon prevents cytotoxic amyloid aggregation of human amylin☆

Oleuropein aglycone protects against pyroglutamylated-3 amyloid-ß toxicity: biochemical, epigenetic and functional correlates

“…After 4 hours of incubation in the presence or in the absence of OLE, the spectra of pE3-Aß displayed a similar trend (Fig. 1C), but in the absence of OLE the signal was considerably reduced, suggesting peptide precipitation, in agreement with previous data relative to human islet amyloid polypeptide aggregation in the presence or in the absence of OLE (Rigacci et al, 2010). Therefore, our findings confirm previous data on Aß42 and human islet amyloid polypeptide, suggesting that also in the case of pE3-Aß OLE does not completely inhibit but, rather, modifies the aggregation path.…”

Efficacy of Oleuropein Aglycone in the Treatment of Transthyretin-Amyloidosis

“…We found that the presence of OleA during wt-TTR and L55P-TTR aggregation pathway induced an increase of Trp quenching, suggesting that the effect of OleA in stabilizing meta-stable intermediate states relies on the reduction of the overall surface hydrophobicity of the aggregates ( Figure 2). OleA does not prevent TTR aggregation by itself but, rather, it is effective in counteracting mature fibrils growth, a behaviour comparable with previously data shown with tau [27], amylin [9] and Abeta peptides [10]. The reported data suggest that OleA induces some remodelling of the supramolecular structure of the growing aggregates.…”

“…Our data offer the possibility to validate and optimize the use of OleA as itself or as a starting point to rationally design promising drugs that could enter in a clinical experimental phase. Recently, most of the research on OleA was focused on its anti-amyloidogenic activity, instead it resulted be able: to interfere in vitro with amyloid fibril formation of two proteins, Amylin, or human islet amyloid polypeptide (hIAPP), and Aβ42, associated with type 2 diabetes and Alzheimer's disease (AD), respectively [9,10]; studies in vivo, using C. elegans as a simplified invertebrate model of AD [11], showed that this polyphenol skips the appearance of toxic oligomers promoting peptide aggregation into aggregates devoid of cytotoxicity [12]. Finally, we recently showed that a dietary supplementation of OleA strongly improved the cognitive performance of the TgCRND8 mouse model of AD; mice showed remarkably reduced plaque deposits and microglia migration to the plaques for phagocytosis [13].…”

Protein misfolding and clearance in demyelinating peripheral neuropathies

“…Proteasome activation by oleuroperin 27 or enhanced targeting to proteasome by an USP14 inhibitor 28 both demonstrated cytoprotective effects. In addition, the chemical compounds B2 and B5 identified from a recent drug screen are inducers of aggresome formation that reduce the cytotoxicity mediated by misfolded proteins.…”