02582nas a2200217   4500008004100000020001400041245010300055210006900158260000800227300001600235490000700251520180900258653002602067653001802093653002902111653001602140653001302156100002902169700003602198856013002234       2021                        eng d  a1949-255300aEpigallocatechin-3-gallate modulates tau post-translational modifications and cytoskeletal network0 aEpigallocatechin3gallate modulates tau posttranslational modific  cMAY  a1083 - 10990 v123 aBACKGROUND: 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.10aAlzheimer’s disease10atau glycation10aTau glycation inhibition10atau protein10aTau PTMs1 aSonawane, Shweta, Kishor1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/epigallocatechin-3-gallate-modulates-tau-post-translational-modifications-and-cytoskeletal