title: The Effect of (-)-Epigallo-catechin-(3)-gallate on Amyloidogenic Proteins Suggests a Common Mechanism.
abstract: Studies on the interaction of the green tea polyphenol (-)-Epigallocatechin-3-gallate (EGCG) with fourteen disease-related amyloid polypeptides and prions Huntingtin, Amyloid-beta, alpha-Synuclein, islet amyloid polypeptide (IAPP), Sup35, NM25 and NM4, tau, MSP2, semen-derived enhancer of virus infection (SEVI), immunoglobulin light chains, beta-microglobulin, prion protein (PrP) and Insulin, have yielded a variety of experimental observations. Here, we analyze whether these observations could be explained by a common mechanism and give a broad overview of the published experimental data on the actions of EGCG. Firstly, we look at the influence of EGCG on aggregate toxicity, morphology, seeding competence, stability and conformational changes. Secondly, we screened publications elucidating the biochemical mechanism of EGCG intervention, notably the effect of EGCG on aggregation kinetics, oligomeric aggregation intermediates, and its binding mode to polypeptides. We hypothesize that the experimental results may be reconciled in a common mechanism, in which EGCG binds to cross-beta sheet aggregation intermediates. The relative position of these species in the energy profile of the amyloid cascade would determine the net effect of EGCG on aggregation and disaggregation of amyloid fibrils.
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO, USA.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Andrich
authors.forename: Jan
authors.initials: J
authors.lastname: Bieschke
mesh_terms: D058227:Amyloidogenic Proteins / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D066329:Protein Aggregates; D055503:Protein Multimerization
chemical_list: D058227:Amyloidogenic Proteins; D066329:Protein Aggregates; D002392:Catechin; C045651:epigallocatechin gallate