scholarly journals A green tea polyphenol Epigallocatechin-3-gallate modulates Tau Post-translational modifications and cytoskeletal network

Author(s):  
Shweta Kishor Sonawane ◽  
Subashchandrabose Chinnathambi

AbstractBackgroundAlzheimer’s disease is a type of dementia denoted by progressive neuronal death due to the accumulation of proteinaceous aggregates of Tau. Post-translational modifications like hyperphosphorylation, truncation, glycation, etc. play a pivotal role in Tau pathogenesis. Glycation of Tau aids in paired helical filament formation and abates its microtubule-binding function. The chemical modulators of Tau PTMs, such as kinase inhibitors and antibody-based therapeutics, have been developed, but natural compounds, as modulators of Tau PTMs are not much explored.MethodsWe applied biophysical and biophysical techniques like fluorescence kinetics, SDS-PAGE, western blot analysis and transmission electron microscopy to investigate the impact of EGCG on Tau glycation in vitro. The effect of glycation on cytoskeleton instability and its EGCG-mediated rescue were studied by immunofluorescence in neuroblastoma cells.ResultsEGCG inhibited methyl glyoxal (MG)-induced Tau glycation in vitro. EGCG potently inhibited MG-induced advanced glycation endproducts formation in neuroblastoma cells as well modulated the localization of AT100 phosphorylated Tau in the cells. In addition to preventing the glycation, EGCG enhanced actin-rich neuritic extensions and rescued actin and tubulin cytoskeleton severely disrupted by MG. EGCG maintained the integrity of the Microtubule Organizing Center (MTOC) stabilized microtubules by Microtubule-associated protein RP/EB family member 1 (EB1).ConclusionsWe report EGCG, a green tea polyphenol, as a modulator of in vitro methylglyoxal-induced Tau glycation and its impact on reducing advanced glycation end products in neuroblastoma cells. We unravel unprecedented function of EGCG in remodeling neuronal cytoskeletal integrity.

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2533
Author(s):  
Rackhyun Park ◽  
Minsu Jang ◽  
Yea-In Park ◽  
Yeonjeong Park ◽  
Woochul Jung ◽  
...  

The COVID-19 pandemic has resulted in a huge number of deaths from 2020 to 2021; however, effective antiviral drugs against SARS-CoV-2 are currently under development. Recent studies have demonstrated that green tea polyphenols, particularly EGCG, inhibit coronavirus enzymes as well as coronavirus replication in vitro. Herein, we examined the inhibitory effect of green tea polyphenols on coronavirus replication in a mouse model. We used epigallocatechin gallate (EGCG) and green tea polyphenols containing more than 60% catechin (GTP60) and human coronavirus OC43 (HCoV-OC43) as a surrogate for SARS-CoV-2. Scanning electron microscopy analysis results showed that HCoV-OC43 infection resulted in virion particle production in infected cells. EGCG and GTP60 treatment reduced coronavirus protein and virus production in the cells. Finally, EGCG- and GTP60-fed mice exhibited reduced levels of coronavirus RNA in mouse lungs. These results demonstrate that green tea polyphenol treatment is effective in decreasing the level of coronavirus in vivo.


2021 ◽  
Vol 547 ◽  
pp. 23-28
Author(s):  
Minsu Jang ◽  
Rackhyun Park ◽  
Yea-In Park ◽  
Yeo-Eun Cha ◽  
Ayane Yamamoto ◽  
...  

2020 ◽  
Vol 138 ◽  
pp. 104791 ◽  
Author(s):  
L. Trovò ◽  
C. Fuchs ◽  
R. De Rosa ◽  
I. Barbiero ◽  
M. Tramarin ◽  
...  

2020 ◽  
Vol 35 (2) ◽  
pp. 149-157
Author(s):  
Zhiheng Guo ◽  
Yi Yang ◽  
Yang Shu ◽  
Li Qiao ◽  
Min Peng ◽  
...  

Nanodrug delivery systems have been widely researched to achieve efficient antitumor drug delivery. However, the controlled drug delivery at tumor cells remains the main challenge for antitumor therapy. Herein, a pH and reduction-responsive nanocarrier based on green tea polyphenols was employed as a smart excipient for chemotherapy drug delivery. Paclitaxel, as a chemotherapy drug, was loaded in the nanocarrier, noted as green tea polyphenol/paclitaxel. The green tea polyphenol/paclitaxel kept constant diameter at physiological condition (i.e. pH 7.4), while gradually enlarged at acid environment (pH = 5.5) and the reductive environment. The in vitro paclitaxel release results indicated that the release of paclitaxel from the green tea polyphenol/paclitaxel at pH 7.4 was slow, whereas obviously accelerated at the acid environment (pH = 5.5) and the reductive environment. The in vitro antitumor assay showed more efficient tumor cells inhibition of green tea polyphenol/paclitaxel than free paclitaxel. Meanwhile, due to the proper size (∼100 nm), green tea polyphenol/paclitaxel could effectively accumulate at tumor sites. In the in vivo mice bearing A549 xenograft mouse models, green tea polyphenol/paclitaxel exhibited satisfactory antitumor effect and depressed system toxicity when compared with free paclitaxel, owing to the enhanced paclitaxel accumulation and controlled paclitaxel release in the tumor cells. With simple compositions and satisfactory antitumor effects, this green tea polyphenol-based nanocarrier can be a promising nanodrug delivery system for the therapy of cancers.


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