Natural polyphenols inhibit different steps of the process of transthyretin (TTR) amyloid fibril formation

作者：Ferreira Nelson; Saraiva Maria Joao; Almeida Maria Rosario^*

来源：FEBS LETTERS, 2011, 585(15): 2424-2430.

DOI：10.1016/j.febslet.2011.06.030

• Transthyretin
• Amyloid inhibitor
• Fibril formation
• (-)-Epigallocatechin-3-gallate
• Curcumin

Several natural polyphenols with potent inhibitory effects on amyloid fibril formation have been reported. Herein, we studied modulation of transthyretin (TTR) fibrillogenesis by selected polyphenols. We demonstrate that both curcumin and nordihydroguaiaretic acid (NDGA) bind to TTR and stabilize the TTR tetramer. However, while NDGA slightly reduced TTR aggregation, curcumin strongly suppressed TTR amyloid fibril formation by generating small "off-pathway'' oligomers and EGCG maintained most of the protein in a non-aggregated soluble form. This indicates alternative mechanisms of action supported by the occurrence of different non-toxic intermediates. Moreover, EGCG and curcumin efficiently disaggregated pre-formed TTR amyloid fibrils. Our studies, together with the safe toxicological profile of these phytochemicals may guide a novel pharmacotherapy for TTR-related amyloidosis targeting different steps in fibrillogenesis.
Structured summary of protein interactions:
TTR binds to TTR by comigration in gel electrophoresis (View interaction)
TTR binds to TTR by dynamic light sc

• 出版日期2011-8