Naturally occurring polyphenolic inhibitors of amyloid beta aggregation

Churches, Quentin I.; Caine, Joanne M.; Cavanagh, Kate; Epa, V. Chandana; Waddington, Lynne J.; Tranberg, C. Elisabet; Meyer, Adam G.; Varghese, J.N.; Streltsov, V.A.; Duggan, Peter J.

doi:10.1016/j.bmcl.2014.05.008

Cited by 78 publications

(58 citation statements)

References 28 publications

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“…Molecular dynamic simulations have also usually been utilized to provide an atomistic explanation of the interactions between an intact polyphenol and polypeptide chains in the amyloid inhibition [40], [41], [42]. The data presented herein suggest that the oxidation of a polyphenol should be considered adequately in its anti-amyloidogenic actions.…”

Section: Discussionmentioning

confidence: 99%

Oxidized epigallocatechin gallate inhibited lysozyme fibrillation more strongly than the native form

Feng

Zeng

2017

Redox Biology

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Epigallocatechin gallate (EGCG), the most abundant flavanoid in green tea, is currently being evaluated in the clinic due to its benefits in the treatment of amyloid disorders. Its anti-amyloidogenic effect has been attributed to direct interaction of the intact molecule with misfolded polypeptides. In addition, antioxidant activity is also involved in the anti-amyloidogenic role. The detailed molecular mechanism is still unclear and requires further investigation. In the present study, the kinetics of EGCG oxidation and the anti-amyloidogenic effect of the resultant oxidation substances have been examined. The results indicate that EGCG degrades in a medium at pH 8.0 with a half-life less than 2 h. By utilizing lysozyme as an in vitro model, the oxidized EGCG demonstrates a more potent anti-amyloidogenic capacity than the intact molecule, as shown by ThT and ANS fluorescence, TEM determination, and hemolytic assay. The oxidized EGCG also has a stronger disruptive effect on preformed fibrils than the native form. Ascorbic acid eliminates the disruptive role of native EGCG on the fibrils, suggesting that oxidation is a prerequisite in fibril disruption. The results of this work demonstrate that oxidized EGCG plays a more important role than the intact molecule in anti-amyloidogenic activity. These insights into the action of EGCG may provide a novel route to understand the anti-amyloidogenic activity of natural polyphenols.

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Section: Discussionmentioning

confidence: 99%

Oxidized epigallocatechin gallate inhibited lysozyme fibrillation more strongly than the native form

Feng

Zeng

2017

Redox Biology

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“…In their study, Sharoar, Thapa [28] found that the glycosylated form of kæmpferol, keampferol-3-o-rhamnoside, abrogates beta amyloid toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates. In another study carried out with 25 phenolic compounds, (not including kæmpferol), Churches, Caine [29] found that luteolin and transilitin display the highest inhibitory power against Aβ fibrillization. Our DLS results show that ARE also interferes with the aggregation path of Aβ 42 .…”

Section: Discussionmentioning

confidence: 99%

Allium roseum L. extract inhibits amyloid beta aggregation and toxicity involved in Alzheimer’s disease

Boubakri

Leri

Bucciantini

et al. 2019

Preprint

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27Allium roseum is an important medicinal and aromatic plant, specific to the North African flora 28 and a rich source of important nutrients and bioactive molecules including flavonoids and 29 organosulfur compounds whose biological activities and pharmacological properties are well known. 30 In the present study, the inhibition of amyloid beta protein toxicity by the ethanolic extract of this 31 plant is investigated for the first time. Preliminary biochemical analyses identified kaempferol and 32 Luteolin-7-o-glucoside as the more abundant phenolic compounds. The effects of A. roseum extract 33 (ARE) on amyloid beta-42 (Aβ 42 ) aggregation and aggregate cytotoxicity, were investigated by 34 biophysical (ThT assay, Dynamic light scattering and transmission electron microscopy) and cellular 35 assays (cytotoxicity, aggregate immunolocalization, ROS measurement and intracellular 36Ca 2+ imaging). The biophysical data suggest that ARE affects the structure of Aβ 42 peptide, inhibits 37 its polymerization, and interferes with the path of fibrillogenesis. The data with cultured cells shows 38 that ARE reduces Aß 42 aggregate toxicity by inhibiting aggregate binding to the cell membrane and 39 by decreasing both oxidative stress and intracellular Ca 2+ . Accordingly, ARE could act as a 40 neuroprotective factor against Aβ aggregate toxicity in Alzheimer's disease. 41 42 Alzheimer's disease. 3 44 1. Introduction 45 Alzheimer's disease (AD), the main cause of senile dementia, is a progressive 46 neurodegenerative disorder associated with cognitive impairment and loss of neuronal cells affecting 47 over 25 million people worldwide [1], thus representing a heavy economic burden and a major health 48problem. The pathology is characterized by the accumulation in the brain of amyloid-β peptide (Aβ) 49 and hyperphosphorylated tau protein mainly found as extracellular senile plaques and intracellular 50 neurofibrillary tangles, respectively [2]. Aβ oligomers overproduction caused by mutations in APP 51 and presenilins [3, 4] appears to be directly associated to cognitive dysfunction and neurodegeneration 52 in AD [5]. Accordingly, toxic Aβ oligomers production and/or interaction with nerve cells appear 53 useful targets to reduce neuronal cell dysfunction. Feart, Samieri [6] suggest that in most cases AD is 54 affected by a combination of genetic and environmental risk factors, including physical activity and 55 nutrition; in particular, increasing evidence indicates that diet plays an important role in AD. Several 56 studies have associated plant food (i.e., vegetables, fruits, legumes, and cereals) consumption to 57 reduced risk of AD [7, 8]. Moreover, traditional medicine is increasingly appreciated as a useful 58 approach to treat many illnesses, and large funds are invested to explore the therapeutic potential of 59 medicinal plants. Fortunately, the search of active compounds from nature prospers and the results 60 increasingly obtained confirm the need to better known the therapeutic potential of these natur...

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“…[3][4][5] Some flavonoids have also exhibited antiaggregative and cytoprotective effects, which may be useful in developing treatments for AD. [5][6][7][8][9][10][11][12] Biflavonoids consist of flavonoid dimers connected by C-C or C-O-C bonds. These molecules occur naturally in gymnosperms and pteridophytes.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory activities of biflavonoids against amyloid-β peptide 42 cytotoxicity in PC-12 cells

Sasaki

Kitoh

Tsukada

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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Naturally occurring polyphenolic inhibitors of amyloid beta aggregation

Cited by 78 publications

References 28 publications

Oxidized epigallocatechin gallate inhibited lysozyme fibrillation more strongly than the native form

Oxidized epigallocatechin gallate inhibited lysozyme fibrillation more strongly than the native form

Allium roseum L. extract inhibits amyloid beta aggregation and toxicity involved in Alzheimer’s disease

Inhibitory activities of biflavonoids against amyloid-β peptide 42 cytotoxicity in PC-12 cells

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