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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2011

Autores

Nelson Ferreira (Autor) Outra; Maria Joao Saraiva (Autor) ICBAS; Maria Rosario Almeida (Autor) ICBAS

Revista

Título: FEBS Letters

Vol. 585

Páginas: 2424-2430

ISSN: 0014-5793

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 121 Citações

Scopus - 127 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Ciências biológicas

Outras Informações

ID Authenticus: P-002-PBN

DOI: 10.1016/j.febslet.2011.06.030

Abstract (EN): 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 scattering (View interaction) TTR binds to TTR by electron microscopy (View interaction)

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7