Oleuropein and derivatives from olives as Tau aggregation inhibitors

Daccache, Anthony; Lion, Cédric; Sibille, Nathalie; Gérard, Melanie; Slomianny, Christian; Lippens, Guy; Cotelle, Philippe

doi:10.1016/j.neuint.2011.02.010

Cited by 146 publications

(98 citation statements)

References 45 publications

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“…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.…”

Section: Oleuropein Aglycone Reduces Transthyretin Fibrils Formationsupporting

confidence: 85%

Efficacy of Oleuropein Aglycone in the Treatment of Transthyretin-Amyloidosis

Leri¹,

Bucciantini²

2016

Biochem Mol Biol J

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Section: Oleuropein Aglycone Reduces Transthyretin Fibrils Formationsupporting

confidence: 85%

Efficacy of Oleuropein Aglycone in the Treatment of Transthyretin-Amyloidosis

Leri¹,

Bucciantini²

2016

Biochem Mol Biol J

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“…The former three sites correspond to the AT8 epitope, as recently redefined on the basis of the AT8 Fab crystal structure in complex with the triply phosphorylated peptide (15), and hence suggest the antibody, clinically used to stage the disease progression (10), indeed immunostains a Tau species that can aggregate without any other factors. Whereas the quest for aggregation inhibitors has been mainly performed with heparin as an external aggregation inducer (46)(47)(48)(49), our present description of a phosphorylation-driven Tau aggregation assay opens up new avenues and should allow retesting of the previously defined classes of molecules or the discovery of potentially more specific molecules that counteract the aggregation of phosphorylated Tau.…”

Section: Discussionmentioning

confidence: 99%

Identification of the Tau phosphorylation pattern that drives its aggregation

Despres

Byrne

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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185

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Determining the functional relationship between Tau phosphorylation and aggregation has proven a challenge owing to the multiple potential phosphorylation sites and their clustering in the Tau sequence. We use here in vitro kinase assays combined with NMR spectroscopy as an analytical tool to generate well-characterized phosphorylated Tau samples and show that the combined phosphorylation at the Ser202/Thr205/Ser208 sites, together with absence of phosphorylation at the Ser262 site, yields a Tau sample that readily forms fibers, as observed by thioflavin T fluorescence and electron microscopy. On the basis of conformational analysis of synthetic phosphorylated peptides, we show that aggregation of the samples correlates with destabilization of the turn-like structure defined by phosphorylation of Ser202/Thr205.

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“…The potential of OLE in the context of AD is corroborated also by its ability to inhibit the fibrillization of tau (both wild-type and carrying the P301L mutation, a mutation that increases its aggregation propensity and leads to frontotemporal dementia and parkinsonism in carriers) leading to reduced deposition of fibrillar material in the form of short rods (TEM analysis) (Daccache et al 2011). The IC50 of OLE for the inhibition of P301L tau aggregation was 1.3 M, as determined by the Thioflavin-S (ThS) fluorescence assay; in contrast, HT was poorly effective, inducing the growth of fibrils that were less dense but structurally similar to those originated in the absence of any inhibitor, thus confirming the superiority of the secoiridoid as an anti-amyloid agent.…”

Section: 3mentioning

confidence: 99%

Olive Oil Phenols as Promising Multi-targeting Agents Against Alzheimer’s Disease

Rigacci

2015

Advances in Experimental Medicine and Biology

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Amyloid diseases are characterized by the deposition of typically aggregated proteins/peptides in tissues, associated with degeneration and progressive functional impairment. Alzheimer's disease is one of the most studied neurodegenerative amyloid diseases and, in Western countries, a significant cause of dementia in the elderly. The so-called "Mediterranean diet" has been considered for long as the healthier dietary regimen, characterised by a great abundance in vegetables and fruits, extra virgin olive oil as the main source of fat, a moderate consumption of red wine and a reduced intake of proteins from red meat. Recent epidemiological studies support the efficacy of the Mediterranean diet not only against cardiovascular and cancer diseases (as previously demonstrated) but also against the cognitive decline associated with ageing, and several data are highlighting the role played by natural phenols, of which red wine and extra virgin olive oil are rich, in such context. In the meantime, studies conducted both in vivo and in vitro have started to reveal the great potential of the phenolic component of extra virgin olive oil (mainly oleuropein aglycone and oleocanthal) in counteracting amyloid aggregation and toxicity, with a particular emphasis on the pathways involved in the onset and progression of Alzheimer's disease: amyloid precursor protein processing, amyloid-beta (Aβ) peptide and tau aggregation, autophagy impairment, neuroinflammation. The aim of this review is to summarize the results of such research efforts, showing how the action of these phenols goes far beyond their renowned antioxidant activity and revealing their potential as multi-targeting agents against Alzheimer's disease.

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Oleuropein and derivatives from olives as Tau aggregation inhibitors

Cited by 146 publications

References 45 publications

Efficacy of Oleuropein Aglycone in the Treatment of Transthyretin-Amyloidosis

Efficacy of Oleuropein Aglycone in the Treatment of Transthyretin-Amyloidosis

Identification of the Tau phosphorylation pattern that drives its aggregation

Olive Oil Phenols as Promising Multi-targeting Agents Against Alzheimer’s Disease

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