The polyphenol EGCG bundles and aggregates hen egg white lysozyme amyloid fibrils at neutral but not acidic pH
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چکیده
Many diseases, including diabetes mellitus and Alzheimer’s disease, are related to accumulation of aggregated (poly)peptides in tissues. These aggregates called amyloids are insoluble and up till now no adequate treatment of amyloid-related diseases is available. One of the most promising therapeutic agents is the polyphenol epigallocatechin-3-gallate (EGCG). It has been shown that EGCG inhibits amyloid formation for various peptides, often resulting in non-toxic oligomers. However, the mechanism behind the interactions between peptides and EGCG remains unclear. Also the knowledge on the effect of EGCG on mature amyloid fibrils is still limited. We investigated the effect of EGCG on amyloid fibrils formed from the model protein hen egg white lysozyme (HEWL) at neutral and acidic pH. We observe that at acidic pH EGCG does not affect the morphology or rigidity of HEWL amyloids fibrils. However, at neutral pH a subpopulation of thick fibrils was formed upon EGCG treatment. Electron microscopy imaging revealed that the thick fibrils formed large fibril aggregates. We show that the solution pH is an important factor in controlling the efficacy of EGCG as a therapeutic agent. EGCG bundles and aggregates amyloid fibrils 143
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