How oxidized EGCG remodels α-synuclein fibrils into non-toxic aggregates: insights from computational simulations

Gonçalves, Priscila Baltazar; Palhano, Fernando L.; Cordeiro, Yraima; Sodero, Ana Carolina Rennó

doi:10.1039/d3cp02261g

Cited by 3 publications

(1 citation statement)

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“…(-)-epigallocatechin-3-gallate (EGCG) is the main molecule in green tea extracts with extensive biological activities [ 15 ]. Recent studies from computational simulations revealed that EGCG attenuates the α-syn protofibril-membrane interactions by forming interactions with the model membrane, thus restoring the membrane integrity, and that oxidized EGCG remodels the toxic α-syn fibrils into non-toxic aggregates by non-covalent interactions [ 16 , 17 ]. These results suggest that EGCG exerts neuroprotective effects, being potentially effective in delaying PD development.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective effect of green tea extract (-)-epigallocatechin-3-gallate in a preformed fibril-induced mouse model of Parkinson’s disease

Shen,

Xie,

et al. 2024

NeuroReport

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Parkinson’s disease (PD) is the second most common neurodegenerative disease characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN). The main bioactive component of green tea polyphenols (-)-epigallocatechin-3-gallate (EGCG) exerts protective effects against diseases such as neurodegenerative diseases and cancer. Therefore, this study investigated the effect of EGCG on the amelioration of neural damage in a chronic PD mouse model induced by α-synuclein preformed fibrils (α-syn-PFFs). A total of 20 C57BL/6J female mice were randomly divided into 3 groups: control group (saline, n = 6), model group (PFFs, n = 7), and prevention group (EGCG+PFFs, n = 7). A chronic PD mouse model was obtained by the administration of α-syn-PFFs by stereotaxic localization in the striatum. Behavioral tests were performed to evaluate PD-related anxiety-like behavior and motor impairments in the long-term PD progression. Tyrosine hydroxylase (TH) immuno-positive neurons and Ser129-phosphorylated α-syn (p-α-syn) were identified by immunohistochemistry. Pro-inflammatory and anti-inflammatory cytokines were measured by real-time quantitative PCR. EGCG pretreatment reduced anxiety-like behavior and motor impairments as revealed by the long-term behavioral test (2 weeks, 1 month, 3 months, and 6 months) on PD mice. EGCG also ameliorated PFF-induced degeneration of TH immuno-positive neurons and accumulation of p-α-syn in the SN and striatum at 6 months. Additionally, EGCG reduced the expression of pro-inflammatory cytokines while promoting the release of anti-inflammatory cytokines. EGCG exerts a neuroprotective effect on long-term progression of the PD model.

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Section: Introductionmentioning

confidence: 99%

Neuroprotective effect of green tea extract (-)-epigallocatechin-3-gallate in a preformed fibril-induced mouse model of Parkinson’s disease

Shen,

Xie,

et al. 2024

NeuroReport

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Effect of flavonoids on the destabilization of α-synuclein fibrils and their conversion to amorphous aggregate: A molecular dynamics simulation and experimental study

Jahan

Ahmad

Deep

2023

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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Understanding the mechanisms of green tea EGCG against amyloid β oligomer neurotoxicity through computational studies

Gonçalves,

Cordeiro,

Rennó Sodero

2024

RSC Adv.

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How oxidized EGCG remodels α-synuclein fibrils into non-toxic aggregates: insights from computational simulations

Abstract: The misfolding and aggregation of the presynaptic protein α-synuclein (α-syn) is a pathological hallmark of Parkinson’s disease (PD). Targeting α-syn has emerged as a promising therapeutic strategy for PD. Emerging...

Cited by 3 publications

References 59 publications

Neuroprotective effect of green tea extract (-)-epigallocatechin-3-gallate in a preformed fibril-induced mouse model of Parkinson’s disease

Neuroprotective effect of green tea extract (-)-epigallocatechin-3-gallate in a preformed fibril-induced mouse model of Parkinson’s disease

Effect of flavonoids on the destabilization of α-synuclein fibrils and their conversion to amorphous aggregate: A molecular dynamics simulation and experimental study

Understanding the mechanisms of green tea EGCG against amyloid β oligomer neurotoxicity through computational studies

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