(−)-Epigallocatechin-3-gallate Inhibits Fibrillogenesis of Chicken Cystatin

Wang, Na; He, Jing; Chang, Alan K.; Wang, Yu; Xu, Linan; Chong, Xiaoying; Lu, Xiaoping; Sun, Yonghui; Xia, Xichun; Li, Hui; Zhang, Bing; Song, Yue; Kato, Akio; Jones, Gary W.

doi:10.1021/jf505277e

Cited by 17 publications

(12 citation statements)

References 28 publications

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“…Curcumin and kaempferol have also been suggested to have similar π-π interactions with this residue [ 19 ]. The fact that taxifolin has displayed a binding to the aggregation-prone HEWL β-domain has also been reported in previous studies investigating other polyphenols, including myricetin [ 18 ], curcumin [ 19 , 58 ], kaempferol [ 19 ], quercetin, and resveratrol [ 59 ]. Interestingly, the interaction with Asn59 and Trp62 in the aggregation-prone β-domain of HEWL could explain the conformational changes detected by anisotropy measurement( Table 3 ).…”

Section: Resultssupporting

confidence: 65%

“…There are many reports demonstrating that polyphenols are effective inhibitors of protein fibrillation [ 12 , 13 , 17 – 20 ], through interaction with one or more of the amyloidogenic species, produced during the course of the aggregation process. For instance, some polyphenols prevent amyloid formation by interacting with and stabilizing native structure of proteins [ 47 , 58 , 61 ]; while others bind to prefibrillar structures and redirect amyloidogenic polypeptides into unstructured, off-pathways oligomers [ 62 ], or toward an alternative non-toxic disordered (amorphous) aggregation pathway [ 20 ]. Recently, Hirohata et al .…”

Section: Resultsmentioning

confidence: 99%

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Inhibition of HEWL fibril formation by taxifolin: Mechanism of action

et al. 2017

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Among therapeutic approaches for amyloid-related diseases, attention has recently turned to the use of natural products as effective anti-aggregation compounds. Although a wealth of in vitro and in vivo evidence indicates some common inhibitory activity of these compounds, they don’t generally suggest the same mechanism of action. Here, we show that taxifolin, a ubiquitous bioactive constituent of foods and herbs, inhibits formation of HEWL amyloid fibrils and their related toxicity by causing formation of very large globular, chain-like aggregates. A range of amyloid-specific techniques were employed to characterize this process. We found that taxifolin exerts its effect by binding to HEWL prefibrillar species, rather than by stabilizing the molecule in its native-like state. Furthermore, it’s binding results in diverting the amyloid pathway toward formation of very large globular, chain-like aggregates with low β-sheet content and reduced solvent-exposed hydrophobic patches. ThT fluorescence measurements show that the binding capacity of taxifolin is significantly reduced, upon generation of large protofibrillar aggregates at the end of growth phase. We believe these results may help design promising inhibitors of protein aggregation for amyloid-related diseases.

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Section: Resultssupporting

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Inhibition of HEWL fibril formation by taxifolin: Mechanism of action

et al. 2017

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“…Further addition of vitamin k3 to preformed HEWL amyloid fibrils did not lead to decrease in ThT fluorescence intensity, it suggests that vitamin k3 cannot reverse the fibril formation but can only inhibit its formation. These results revealed that vitamin k3 inhibits fibrillation from very beginning of log phase as observed in the case of EGCG which inhibits fibrillogenesis of Chicken Cystatin 29 .…”

Section: Resultsmentioning

confidence: 55%

Vitamin k3 inhibits protein aggregation: Implication in the treatment of amyloid diseases

Alam

Chaturvedi

Siddiqi

et al. 2016

Sci Rep

162

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Protein misfolding and aggregation have been associated with several human diseases such as Alzheimer’s, Parkinson’s and familial amyloid polyneuropathy etc. In this study, anti-fibrillation activity of vitamin k3 and its effect on the kinetics of amyloid formation of hen egg white lysozyme (HEWL) and Aβ-42 peptide were investigated. Here, in combination with Thioflavin T (ThT) fluorescence assay, circular dichroism (CD), transmission electron microscopy and cell cytotoxicity assay, we demonstrated that vitamin k3 significantly inhibits fibril formation as well as the inhibitory effect is dose dependent manner. Our experimental studies inferred that vitamin k3 exert its neuro protective effect against amyloid induced cytotoxicity through concerted pathway, modifying the aggregation formation towards formation of nontoxic aggregates. Molecular docking demonstrated that vitamin k3 mediated inhibition of HEWL and Aβ-42 fibrillogenesis may be initiated by interacting with proteolytic resistant and aggregation prone regions respectively. This work would provide an insight into the mechanism of protein aggregation inhibition by vitamin k3; pave the way for discovery of other small molecules that may exert similar effect against amyloid formation and its associated neurodegenerative diseases.

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“…TEM is generally used to observe and prove the morphology of aggregates qualitatively (Wang et al 2015;Sun et al 2016). TEM images in Fig.…”

Section: Morphologies Of As Aggregatesmentioning

confidence: 99%

Metal chelator EGCG attenuates Fe(III)‐induced conformational transition of α‐synuclein and protects AS‐PC12 cells against Fe(III)‐induced death

Zhao

Liang

et al. 2017

Journal of Neurochemistry

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The fibrillation and aggregation of α-synuclein (AS), along with the conformational transition from random coil to β-sheet, are the critical steps in the development of Parkinson's disease (PD). It is acknowledged that iron accumulation in the brain may lead to the fibrillation of AS. However, (-)-epigallocatechin gallate (EGCG) can penetrate the blood-brain barrier, chelate metal ions, and inhibit the fibrillation of amyloid proteins. Therefore, EGCG is warranted to be investigated for its potential to cure amyloid-related diseases. In the present work, we sought to study the effects of EGCG on Fe(III)-induced fibrillation of AS on both molecular and cellular levels. We demonstrate that Fe(III) interacts with the amino residue of Tyr and Ala of AS, then accelerates the fibrillation of AS, and increases intracellular reactive oxygen species (ROS) in the AS transduced-PC12 cells (AS-PC12 cells). However, EGCG significantly inhibits this process by chelating Fe(III) and protects AS-PC12 cells against the toxicity induced by ROS and β-sheet-enriched AS fibrils. These findings yield useful information that EGCG might be a promising drug to prevent and treat the neurodegenerative diseases.

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(−)-Epigallocatechin-3-gallate Inhibits Fibrillogenesis of Chicken Cystatin

Cited by 17 publications

References 28 publications

Inhibition of HEWL fibril formation by taxifolin: Mechanism of action

Inhibition of HEWL fibril formation by taxifolin: Mechanism of action

Vitamin k3 inhibits protein aggregation: Implication in the treatment of amyloid diseases

Metal chelator EGCG attenuates Fe(III)‐induced conformational transition of α‐synuclein and protects AS‐PC12 cells against Fe(III)‐induced death

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