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 μM.
Highlights
Tau aggregation and accumulation is a key event in the pathogenesis of Alzheimer’s disease
Full-length Tau and EGCG binding was determined by using isothermal titration calorimetry
The heat plot between the heat change per mole of the reactants EGCG and Tau and their molar ratio gives the number of interacting sites as 3.48 (Fig. 1D) and the Kd was determined from the thermodynamic parameters as 74 nM (Table 1)
Summary
Tau aggregation and accumulation is a key event in the pathogenesis of Alzheimer’s disease. 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 misfolded proteins involved in Alzheimer’s disease (AD) are amyloid-β (Aβ) and Tau (Fig. 1A) whereas[5]; α-Synuclein is a key player in Parkinson’s disease. The phenothiazine compounds inhibit Tau-Tau (repeat domain) binding preventing Tau aggregation. EGCG has been implicated in preventing aggregation of proteins involved in disease c onditions[27]
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