Polyphenols in combination with β-cyclodextrin can inhibit and disaggregate α-synuclein amyloids under cell mimicking conditions: A promising therapeutic alternative

Gautam, Saurabh; Karmakar, Sandip; Batra, Renu; Sharma, Pankaj; Pradhan, Prashant; Singh, Jasdeep; Kundu, Bishwajit; Chowdhury, P. K.

doi:10.1016/j.bbapap.2017.02.014

Cited by 54 publications

(53 citation statements)

References 70 publications

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“…; Gautam et al . ) to have anti‐cancer and anti‐oxidative capabilities. The vicinal poly‐hydroxyphenyl OH groups in polyphenolic compounds play a vital role in inhibition of amyloids (Meng et al .…”

Section: Discussionmentioning

confidence: 99%

“…Many small natural polyphenols, such as resveratrol, curcumin, baicalein, etc. for the inhibition of amyloid formation of AS have been reported (Caruana et al 2011;Gautam et al 2017) to have anti-cancer and anti-oxidative capabilities. The vicinal poly-hydroxyphenyl OH groups in polyphenolic compounds play a vital role in inhibition of amyloids (Meng et al 2009).…”

Section: Effect Of Egcg On As Fibrillationmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Effect Of Egcg On As Fibrillationmentioning

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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“…These in turn, show the potential application of polyphenols in the treatment of cancer, obesity and cardiovascular disease. In addition, polyphenols of plant origin are becoming popular choices for food supplements (Gautam et al, ; Ghanemi et al, ). Therefore, researchers in various fields, including pharmaceuticals, food industries, cosmetics and agricultural sectors, are showing increased interest in the study of polyphenols (Gautam et al, ; Márcio et al, ; Zhao et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, polyphenols of plant origin are becoming popular choices for food supplements (Gautam et al, ; Ghanemi et al, ). Therefore, researchers in various fields, including pharmaceuticals, food industries, cosmetics and agricultural sectors, are showing increased interest in the study of polyphenols (Gautam et al, ; Márcio et al, ; Zhao et al, ). Humulus japonicus Siebold & Zucc is a perennial medicinal herb from the Cannabaceae family (also called the Hemp family; Čeh, Milica, Iztok, & Veronika, ).…”

Section: Introductionmentioning

confidence: 99%

LC‐MS/MS profiling of polyphenol‐enriched leaf, stem and root extracts of Korean Humulus japonicus Siebold & Zucc and determination of their antioxidant effects

Choi

Desta

Lee

et al. 2018

Biomedical Chromatography

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Polyphenols from ethyl acetate extracts from the leaves, stems and roots of Korean Humulus japonicus were comprehensively profiled using liquid chromatography-electrospray ionization-tandem mass spectrometry. A total of 36 polyphenols were detected, of which 26 were structurally characterized based on their [M - H] peak, tandem mass spectrometry fragmentation pattern, UV-vis absorption and published data. Validation data provided satisfactory results for the evaluated parameters. The determination coefficients were ≥0.9812. The limits of detection and quantification were 0.017-0.573 and 0.056-1.834 mg/L, respectively, indicating good performance limits. The accuracy (expressed as percentage recovery) at 50 and 100 mg/L was 71.4-99.7 and 75.1-105.1%, with precisions (expressed as relative standard deviation) of 1.5-7.3 and 0.8-4.1%, respectively, indicating acceptable accuracy and precision values. The leaves were rich in total polyphenols (3089.9 ± 6.4 mg/kg of fresh sample) followed by the stems (1313.9 ± 6.4 mg/kg of fresh sample) and roots (655.2 ± 2.7 mg/kg of fresh sample). Antioxidant activity, determined by α,α-diphenyl-β-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging activity and ferric reducing antioxidant power assay, revealed the lowest EC value for the leaf extracts, indicating a higher scavenging activity in this tissue followed by the roots and stems. Overall, the results indicated that H. japonicus is rich in polyphenols and could be a potential alternative to Humulus lupulus (hop plant) in the brewery industry.

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“…The anti-aggregative effect of curcumin occurred through interaction of the molecule to the hydrophobic NAC domain of α-syn via both hydrophobic and hydrogen bonding [363,364]. Curcumin interacted with both α-syn monomers and oligomers via its phenolic groups [365], but was found to preferentially bind oligomeric intermediates [360]. Conformational changes of α-syn affected the extent of binding of curcumin to α-syn and its potential in inhibiting oligomers or fibrils [360,364,366].…”

Section: Polyphenolsmentioning

confidence: 99%

Targeting α-Synuclein for PD Therapeutics: A Pursuit on All Fronts

et al. 2020

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Parkinson’s Disease (PD) is characterized both by the loss of dopaminergic neurons in the substantia nigra and the presence of cytoplasmic inclusions called Lewy Bodies. These Lewy Bodies contain the aggregated α-synuclein (α-syn) protein, which has been shown to be able to propagate from cell to cell and throughout different regions in the brain. Due to its central role in the pathology and the lack of a curative treatment for PD, an increasing number of studies have aimed at targeting this protein for therapeutics. Here, we reviewed and discussed the many different approaches that have been studied to inhibit α-syn accumulation via direct and indirect targeting. These analyses have led to the generation of multiple clinical trials that are either completed or currently active. These clinical trials and the current preclinical studies must still face obstacles ahead, but give hope of finding a therapy for PD with time.

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Polyphenols in combination with β-cyclodextrin can inhibit and disaggregate α-synuclein amyloids under cell mimicking conditions: A promising therapeutic alternative

Cited by 54 publications

References 70 publications

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

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

LC‐MS/MS profiling of polyphenol‐enriched leaf, stem and root extracts of Korean Humulus japonicus Siebold & Zucc and determination of their antioxidant effects

Targeting α-Synuclein for PD Therapeutics: A Pursuit on All Fronts

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