Oncotarget

Research Papers:

Epigallocatechin-3-gallate modulates Tau Post-translational modifications and cytoskeletal network

Shweta Kishor Sonawane and Subashchandrabose Chinnathambi _

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Oncotarget. 2021; 12:1083-1099. https://doi.org/10.18632/oncotarget.27963

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Abstract

Shweta Kishor Sonawane1,2 and Subashchandrabose Chinnathambi1,2

1 Neurobiology Group, Biochemical Sciences Division, CSIR-National Chemical Laboratory, Pune 411008, India

2 Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India

Correspondence to:

Subashchandrabose Chinnathambi,email: s.chinnathambi@ncl.res.in

Keywords: Alzheimer’s disease; Tau protein; Tau PTMs; Tau glycation; Tau glycation inhibition

Received: June 02, 2020     Accepted: May 05, 2021     Published: May 25, 2021

Copyright: © 2021 Sonawane and Chinnathambi. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Background: Alzheimer’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.

Materials and Methods: We applied biophysical and biochemical techniques like fluorescence kinetics, oligomerization 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 microscopy in neuroblastoma cells.

Results: EGCG 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).

Conclusions: We 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.


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