Distinguishing the Effect on the Rate and Yield of A?42 Aggregation by Green Tea Polyphenol EGCG.

ABSTRACT: Deposition of A?42 aggregates in the form of amyloid plaques is a pathological hallmark of Alzheimer's disease. A desired avenue of intervention is the inhibition of A?42 aggregation. Epigallocatechin gallate (EGCG), the main polyphenol in green tea, has been generally considered an inhibitor of A? aggregation. However, previous experiments focused on the reduction of the amount of A?42 aggregates, while the effect of EGCG on the rate of A?42 aggregation was not critically analyzed. Here we performed an experimental evaluation of A?42 aggregation kinetics in the absence and presence of EGCG at a wide range of concentrations. We found that EGCG reduced thioflavin T fluorescence in an EGCG concentration-dependent manner, suggesting that EGCG reduced the amount of A?42 fibrils. The effect of EGCG on the rate of A?42 aggregation appears to be bimodal. We found that higher EGCG-to-A?42 ratios promoted the rate of A?42 aggregation, while lower EGCG-to-A?42 ratios inhibited the aggregation rate. To confirm that the reduction of thioflavin T fluorescence is due to the lowered aggregate quantity, but not due to perturbation of thioflavin T binding to A?42 fibrils, we probed the effect of EGCG on A?42 aggregation using site-directed spin labeling. Electron paramagnetic resonance of spin-labeled A?42 aggregates suggests that high EGCG-to-A?42 ratios led to a greatly reduced amount of A?42 fibrils, and these aggregates adopt similar structures as the fibrils in the no-EGCG sample. Potential implications of this work in designing prevention or therapeutic strategies using EGCG are discussed.

SUBMITTER: Park G 

PROVIDER: S-EPMC7469419 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature