Binding of epigallocatechin-3-gallate to transthyretin modulates its amyloidogenicity.
More than 100 transthyretin (TTR) variants are associated with hereditary amyloidosis. Approaches for TTR amyloidosis that interfere with any step of the cascade of events leading to fibril formation have therapeutic potential. In this study we tested (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin of green tea, as an inhibitor of TTR amyloid formation. We demonstrate that EGCG binds to TTR "in vitro" and "ex vivo" and that EGCG inhibits TTR aggregation "in vitro" and in a cell culture system. These findings together with the low toxicity of the compound raise the possibility of using EGCG in a therapeutic approach for familial amyloidotic polyneuropathy, the most frequent form of hereditary TTR amyloidosis.
Grupo de Neurobiologia Molecular, Instituto de Biologia Molecular e Celular, 4150-180 Porto, Portugal.
Nelson
N
Ferreira
Isabel
I
Cardoso
Maria Rosário
MR
Domingues
Rui
R
Vitorino
Margarida
M
Bastos
Guangyue
G
Bai
Maria João
MJ
Saraiva
Maria Rosário
MR
Almeida
D019943:Amino Acid Substitution; D000682:Amyloid / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D011228:Prealbumin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D013974:Thyroxine / Q000378:metabolism; D014162:Transfection
D000682:Amyloid; D011228:Prealbumin; D002392:Catechin; C045651:epigallocatechin gallate; D013974:Thyroxine