Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

EGCG impedes human Tau aggregation and interacts with Tau.

ABSTRACT: Tau aggregation and accumulation is a key event in the pathogenesis of Alzheimer's disease. Inhibition of Tau aggregation is therefore a potential therapeutic strategy to ameliorate the disease. Phytochemicals are being highlighted as potential aggregation inhibitors. Epigallocatechin-3-gallate (EGCG) is an active phytochemical of green tea that has shown its potency against various diseases including aggregation inhibition of repeat Tau. The potency of EGCG in altering the PHF assembly of full-length human Tau has not been fully explored. By various biophysical and biochemical analyses like ThS fluorescence assay, MALDI-TOF analysis and Isothermal Titration Calorimetry, we demonstrate dual effect of EGCG on aggregation inhibition and disassembly of full-length Tau and their binding affinity. The IC50 for Tau aggregation by EGCG was found to be 64.2 ?M.

SUBMITTER: Sonawane SK

PROVIDER: S-EPMC7387440 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

EGCG impedes human Tau aggregation and interacts with Tau.

Sonawane Shweta Kishor SK Chidambaram Hariharakrishnan H Boral Debjyoti D Gorantla Nalini Vijay NV Balmik Abhishek Ankur AA Dangi Abha A Ramasamy Sureshkumar S Marelli Udaya Kiran UK Chinnathambi Subashchandrabose S

Scientific reports 20200728 1

Tau aggregation and accumulation is a key event in the pathogenesis of Alzheimer's disease. Inhibition of Tau aggregation is therefore a potential therapeutic strategy to ameliorate the disease. Phytochemicals are being highlighted as potential aggregation inhibitors. Epigallocatechin-3-gallate (EGCG) is an active phytochemical of green tea that has shown its potency against various diseases including aggregation inhibition of repeat Tau. The potency of EGCG in altering the PHF assembly of full- ...[more]

PMID: 32724104

Similar Datasets

Influence of Aluminium and EGCG on Fibrillation and Aggregation of Human Islet Amyloid Polypeptide.

Project description:The abnormal fibrillation of human islet amyloid polypeptide (hIAPP) has been implicated in the development of type II diabetes. Aluminum is known to trigger the structural transformation of many amyloid proteins and induce the formation of toxic aggregate species. The (-)-epigallocatechin gallate (EGCG) is considered capable of binding both metal ions and amyloid proteins with inhibitory effect on the fibrillation of amyloid proteins. However, the effect of Al(III)/EGCG complex on hIAPP fibrillation is unclear. In the present work, we sought to view insight into the structures and properties of Al(III) and EGCG complex by using spectroscopic experiments and quantum chemical calculations and also investigated the influence of Al(III) and EGCG on hIAPP fibrillation and aggregation as well as their combined interference on this process. Our studies demonstrated that Al(III) could promote fibrillation and aggregation of hIAPP, while EGCG could inhibit the fibrillation of hIAPP and lead to the formation of hIAPP amorphous aggregates instead of the ordered fibrils. Furthermore, we proved that the Al(III)/EGCG complex in molar ratio of 1 : 1 as Al(EGCG)(H2O)2 could inhibit the hIAPP fibrillation more effectively than EGCG alone. The results provide the invaluable reference for the new drug development to treat type II diabetes.

| S-EPMC5198260 | biostudies-literature

Using Human iPSC-Derived Neurons to Model TAU Aggregation.

Project description:Alzheimer's disease and frontotemporal dementia are amongst the most common forms of dementia characterized by the formation and deposition of abnormal TAU in the brain. In order to develop a translational human TAU aggregation model suitable for screening, we transduced TAU harboring the pro-aggregating P301L mutation into control hiPSC-derived neural progenitor cells followed by differentiation into cortical neurons. TAU aggregation and phosphorylation was quantified using AlphaLISA technology. Although no spontaneous aggregation was observed upon expressing TAU-P301L in neurons, seeding with preformed aggregates consisting of the TAU-microtubule binding repeat domain triggered robust TAU aggregation and hyperphosphorylation already after 2 weeks, without affecting general cell health. To validate our model, activity of two autophagy inducers was tested. Both rapamycin and trehalose significantly reduced TAU aggregation levels suggesting that iPSC-derived neurons allow for the generation of a biologically relevant human Tauopathy model, highly suitable to screen for compounds that modulate TAU aggregation.

| S-EPMC4697850 | biostudies-literature

Uncovering specificity of endogenous TAU aggregation in a human iPSC-neuron TAU seeding model.

Project description:Tau pathobiology has emerged as a key component underlying Alzheimer's disease (AD) progression; however, human neuronal in vitro models have struggled to recapitulate tau phenomena observed in vivo. Here, we aimed to define the minimal requirements to achieve endogenous tau aggregation in functional neurons utilizing human induced pluripotent stem cell (hiPSC) technology. Optimized hiPSC-derived cortical neurons seeded with AD brain-derived competent tau species or recombinant tau fibrils displayed increases in insoluble, endogenous tau aggregates. Importantly, MAPT-wild type and MAPT-mutant hiPSC-neurons exhibited unique propensities for aggregation dependent on the seed strain rather than the repeat domain identity, suggesting that successful templating of the recipient tau may be driven by the unique conformation of the seed. The in vitro model presented here represents the first successful demonstration of combining human neurons, endogenous tau expression, and AD brain-derived competent tau species, offering a more physiologically relevant platform to study tau pathobiology.

| S-EPMC8761709 | biostudies-literature

TREM2 function impedes tau seeding in neuritic plaques.

Project description:Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been associated with increased risk for sporadic, late-onset Alzheimer's disease. Here we show that germline knockout of Trem2 or the TREM2R47H variant reduces microgliosis around amyloid-? plaques and facilitates the seeding and spreading of neuritic plaque tau aggregates. These findings demonstrate a key role for TREM2 and microglia in limiting the development of peri-plaque tau pathologies.

| S-EPMC6660358 | biostudies-literature

Increased G3BP2-Tau interaction in Tauopathies is a natural defense against Tau aggregation

Project description:Many RNA-binding proteins (RBPs), particularly those associated with RNA granules, promote pathological protein aggregation in neurodegenerative diseases. Here, we demonstrate that G3BP2, a core component of stress granules, directly interacts with Tau and inhibits Tau aggregation. In the human brain, the interaction of G3BP2 and Tau is dramatically increased in multiple Tauopathies and precedes neurofibrillary tangle (NFT) formation in Alzheimer’s disease (AD). Surprisingly, Tau pathology is significantly elevated upon loss of G3BP2 in human neurons and brain organoids. Moreover, we find that G3BP2 masks the microtubule-binding region (MTBR) of Tau, thereby inhibiting Tau aggregation. Our study defines a novel role for RBPs as a line of defense against Tau aggregation in Tauopathies.

2023-05-17 | GSE226624 | GEO

14-3-3? Mediates Tau Aggregation in Human Neuroblastoma M17 Cells.

Project description:Microtubule-associated protein tau is the major component of paired helical filaments (PHFs) associated with the neuropathology of Alzheimer's disease (AD). Tau in the normal brain binds and stabilizes microtubules. Tau isolated from PHFs is hyperphosphorylated, which prevents it from binding to microtubules. Tau phosphorylation has been suggested to be involved in the development of NFT pathology in the AD brain. Recently, we showed that 14-3-3? is bound to tau in the PHFs and when incubated in vitro with 14-3-3?, tau formed amorphous aggregates, single-stranded straight filaments, double stranded ribbon-like filaments and PHF-like filaments that displayed close resemblance with corresponding ultrastructures of AD brain. Surprisingly however, phosphorylated and non-phosphorylated tau aggregated in a similar manner, indicating that tau phosphorylation does not affect in vitro tau aggregation (Qureshi et al (2013) Biochemistry 52, 6445-6455). In this study, we have examined the role of tau phosphorylation in tau aggregation in cellular level. We have found that in human M17 neuroblastoma cells, tau phosphorylation by GSK3? or PKA does not cause tau aggregation, but promotes 14-3-3?-induced tau aggregation by destabilizing microtubules. Microtubule disrupting drugs also promoted 14-3-3?-induced tau aggregation without changing tau phosphorylation in M17 cell. In vitro, when incubated with 14-3-3? and microtubules, nonphosphorylated tau bound to microtubules and did not aggregate. Phosphorylated tau on the other hand did not bind to microtubules and aggregated. Our data indicate that microtubule-bound tau is resistant to 14-3-3?-induced tau aggregation and suggest that tau phosphorylation promotes tau aggregation in the brain by detaching tau from microtubules and thus making it accessible to 14-3-3?.

| S-EPMC4993442 | biostudies-literature

The role of annealing and fragmentation in human tau aggregation dynamics.

Project description:Alzheimer's disease pathogenesis is associated with the conversion of monomeric tau protein into filamentous aggregates. Because both toxicity and prion-like spread of pathogenic tau depend in part on aggregate size, the processes that underlie filament formation and size distribution are of special importance. Here, using a combination of biophysical and computational approaches, we investigated the fibrillation dynamics of the human tau isoform 2N4R. We found that tau filaments engage in a previously uncharacterized secondary process involving end-to-end annealing and that rationalization of empirical aggregation data composed of total protomer concentrations and fibril length distributions requires inclusion of this process along with filament fragmentation. We noted that annealing of 2N4R tau filaments is robust, with an intrinsic association rate constant of a magnitude similar to that mediating monomer addition and consistent with diffusion-mediated protein-protein interactions in the absence of long-range attractive forces. In contrast, secondary nucleation on the surface of tau filaments did not detectably contribute to tau aggregation dynamics. These results indicate that tau filament ends engage in a range of homotypic interactions involving monomers, oligomers, and filaments. They further indicate that, in the case of tau protein, fibril annealing and fragmentation along with primary nucleation and elongation are the major processes controlling filament size distribution.

| S-EPMC6442056 | biostudies-literature

Tau binding protein CAPON induces tau aggregation and neurodegeneration.

Project description:To understand the molecular processes that link Aβ amyloidosis, tauopathy and neurodegeneration, we screened for tau-interacting proteins by immunoprecipitation/LC-MS. We identified the carboxy-terminal PDZ ligand of nNOS (CAPON) as a novel tau-binding protein. CAPON is an adaptor protein of neuronal nitric oxide synthase (nNOS), and activated by the N-methyl-D-aspartate receptor. We observed accumulation of CAPON in the hippocampal pyramidal cell layer in the AppNL-G-F -knock-in (KI) brain. To investigate the effect of CAPON accumulation on Alzheimer's disease (AD) pathogenesis, CAPON was overexpressed in the brain of AppNL-G-F mice crossbred with MAPT (human tau)-KI mice. This produced significant hippocampal atrophy and caspase3-dependent neuronal cell death in the CAPON-expressing hippocampus, suggesting that CAPON accumulation increases neurodegeneration. CAPON expression also induced significantly higher levels of phosphorylated, oligomerized and insoluble tau. In contrast, CAPON deficiency ameliorated the AD-related pathological phenotypes in tauopathy model. These findings suggest that CAPON could be a druggable AD target.

| S-EPMC6546774 | biostudies-literature

Bacterial DNA promotes Tau aggregation.

Project description:A hallmark feature of Alzheimer's disease (AD) and other tauopathies is the misfolding, aggregation and cerebral accumulation of tau deposits. Compelling evidence indicates that misfolded tau aggregates are neurotoxic, producing synaptic loss and neuronal damage. Misfolded tau aggregates are able to spread the pathology from cell-to-cell by a prion like seeding mechanism. The factors implicated in the initiation and progression of tau misfolding and aggregation are largely unclear. In this study, we evaluated the effect of DNA extracted from diverse prokaryotic and eukaryotic cells in tau misfolding and aggregation. Our results show that DNA from various, unrelated gram-positive and gram-negative bacteria results in a more pronounced tau misfolding compared to eukaryotic DNA. Interestingly, a higher effect in promoting tau aggregation was observed for DNA extracted from certain bacterial species previously detected in the brain, CSF or oral cavity of patients with AD. Our findings indicate that microbial DNA may play a previously overlooked role in the propagation of tau protein misfolding and AD pathogenesis, providing a new conceptual framework that positions the compromised blood-brain and intestinal barriers as important sources of microbial DNA in the CNS, opening novel opportunities for therapeutic interventions.

| S-EPMC7012890 | biostudies-literature

Neem Derivatives Inhibits Tau Aggregation.

Project description:Tau is a phosphoprotein with natively unfolded conformation that functions to stabilize microtubules in axons. Alzheimer's disease pathology triggers several modifications in tau, which causes it to lose its affinity towards microtubule, thus, leading to microtubule disassembly and loss of axonal integrity. This elicit accumulation of tau as paired helical filaments is followed by stable neurofibrillary tangles formation. A large number of small molecules have been isolated from Azadirachta indica with varied medicinal applications. The intermediate and final limonoids, nimbin and salannin respectively, isolated from Azadirachta indica, were screened against tau aggregation. ThS and ANS fluorescence assay showed the role of intermediate and final limonoids in preventing heparin induced cross-β sheet formation and also decreased hydrophobicity, which are characteristic nature of tau aggregation. Transmission electron microscopy studies revealed that limonoids restricted the aggregation of tau to fibrils; in turn, limonoids led to the formation of short and fragile aggregates. Both the limonoids were non-toxic to HEK293T cells thus, substantiating limonoids as a potential lead in overcoming Alzheimer's disease.

| S-EPMC6597962 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data