New polyphenols active on β-amyloid aggregation

Rivière, Céline; Richard, Tristan; Vitrac, Xavier; Mérillon, Jean‐Michel; Valls, Josep; Monti, Jean‐Pierre

doi:10.1016/j.bmcl.2007.11.028

Cited by 83 publications

(77 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Polyphenols have potent anti-amyloidogenic and anti-fibril effects in vitro, suggesting that resveratrol may prevent the formation of toxic Aβ oligomers and protofibrillar intermediates (Riviere et al 2008). Moderate consumption of red wine lowered Aβ levels and the associated neuropathology in Tg2576 AD mouse model .…”

Section: Compounds With Predominant Antioxidative Activity Often Accmentioning

confidence: 99%

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

et al. 2012

View full text Add to dashboard Cite

Section: Compounds With Predominant Antioxidative Activity Often Accmentioning

confidence: 99%

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

et al. 2012

View full text Add to dashboard Cite

“…Recent studies have shown that polyphenols have potent anti-amyloidogenic activities in vitro [28][29][30][31][32] and in vivo [33,34]. Polyphenols are natural substances present in beverages obtained from plants, fruits and vegetables such as olive oil, red wine and tea.…”

Section: Introductionmentioning

confidence: 99%

“…In this work, we studied in vitro the effects of polyphenols on the formation and stability of Ab oligomers and fibrils using gel filtration chromatography measurements complemented by electron microscopy (EM) and fluorescence spectroscopy with Thioflavin T. We used the Ab25-35 amino-acid peptide (Ab [25][26][27][28][29][30][31][32][33][34][35], which preserves the properties of neurotoxicity and aggregation [49][50][51], and the polyphenol piceid, which is a good inhibitor of Ab fibril formation [31]. We sought to answer two questions: which molecular step in the polymerization pathway is affected by the polypeptidic inhibitors and what is the mechanism of interaction between Ab and piceid?…”

Section: Introductionmentioning

confidence: 99%

The Polyphenol Piceid Destabilizes Preformed Amyloid Fibrils and Oligomers In Vitro: Hypothesis on Possible Molecular Mechanisms

et al. 2008

Self Cite

View full text Add to dashboard Cite

Alzheimer's disease (AD) is characterized by deposits of amyloid in various tissues. The neuronal cytotoxicity of Abeta peptides is attributed not only to various mechanisms but also to amyloid fibrils and soluble oligomeric intermediates. Consequently, finding molecules to prevent or reverse the oligomerization and fibrillization of Abeta could be of therapeutic value in the treatment of AD. We show that piceid, a polyphenol of the stilbene family, destabilized fibrils and oligomers to give back monomers that are not neurotoxic molecules. The mechanism of this destabilization could be a dynamic interaction between the polyphenol and the Abeta that could open the hydrophobic zipper and shift the reversible equilibrium "random coil<-->beta-sheet" to the disordered structure.

show abstract

“…These descriptors clearly corroborate the empirical findings according to which the hydrophobicity of the molecule plays a central role in the inhibition process. [18,20,41] Furthermore, these findings suggest that hydrogen bonds and hydrophobic interactions are complementary in terms of inhibition ability.…”

Section: Resultsmentioning

confidence: 96%

“…Various unrelated small molecules have been studied and shown to inhibit Ab aggregation and Ab toxicity, both in vitro and in vivo [17][18][19][20]. The aromatic moieties of Ab have been shown to have a central role in the molecular recognition and the self-assembly processes, leading to the formation of Ab fibrils [21].…”

Section: Introductionmentioning

confidence: 99%

Quantitative structure–activity relationship analysis of β-amyloid aggregation inhibitors

Stempler

Levy‐Sakin

Frydman‐Marom

et al. 2010

J Comput Aided Mol Des

View full text Add to dashboard Cite

Inhibiting the aggregation process of the β-amyloid peptide is a promising strategy in treating Alzheimer's disease. In this work, we have collected a dataset of 80 small molecules with known inhibition levels and utilized them to develop two comprehensive quantitative structure-activity relationship models: a Bayesian model and a decision tree model. These models have exhibited high predictive accuracy: 87% of the training and test sets using the Bayesian model and 89 and 93% of the training and test sets, respectively, by the decision tree model. Subsequently these models were used to predict the activities of several new potential β-amyloid aggregation inhibitors and these predictions were indeed validated by in vitro experiments. Key chemical features correlated with the inhibition ability were identified. These include the electro-topological state of carbonyl groups, AlogP and the number of hydrogen bond donor groups. The results demonstrate the feasibility of the developed models as tools for rapid screening, which could help in the design of novel potential drug candidates for Alzheimer's disease.

show abstract

New polyphenols active on β-amyloid aggregation

Cited by 83 publications

References 12 publications

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

The Polyphenol Piceid Destabilizes Preformed Amyloid Fibrils and Oligomers In Vitro: Hypothesis on Possible Molecular Mechanisms

Quantitative structure–activity relationship analysis of β-amyloid aggregation inhibitors

Contact Info

Product

Resources

About