MINT MINT, Dpt of Biology, University of Rome Tor Vergata MINT http://mint.bio.uniroma2.it/mint url>http://mint.bio.uniroma2.it/mint/ https://mint.bio.uniroma2.it MINT-[0-9]+ https://mint.bio.uniroma2.it/index.php/results-interactions/?id=${ac} The Molecular INTeraction database (MINT) is a relational database designed to store interactions between biological molecules. http://mint.bio.uniroma2.it Natural polyphenols inhibit different steps of the process of transthyretin (TTR) amyloid fibril formation. Natural polyphenols inhibit different steps of the process of transthyretin (TTR) amyloid fibril formation. FEBS Lett. (0014-5793) 2011 Ferreira N., Saraiva MJ., Almeida MR. suggested by lperfetto ngomes@ibmc.up.pt in vitro In vitro dls dynamic light scattering dls predetermined predetermined participant predetermined Ferreira N., Saraiva MJ., Almeida MR. suggested by lperfetto ngomes@ibmc.up.pt FEBS Lett. (0014-5793) 2011 Natural polyphenols inhibit different steps of the process of transthyretin (TTR) amyloid fibril formation. Natural polyphenols inhibit different steps of the process of transthyretin (TTR) amyloid fibril formation. FEBS Lett. (0014-5793) 2011 Ferreira N., Saraiva MJ., Almeida MR. suggested by lperfetto ngomes@ibmc.up.pt in vitro In vitro electron microscopy electron microscopy Electron crystallography Electron cryomicroscopy Electron crystallography Electron cryomicroscopy predetermined predetermined participant predetermined Ferreira N., Saraiva MJ., Almeida MR. suggested by lperfetto ngomes@ibmc.up.pt FEBS Lett. (0014-5793) 2011 Natural polyphenols inhibit different steps of the process of transthyretin (TTR) amyloid fibril formation. Natural polyphenols inhibit different steps of the process of transthyretin (TTR) amyloid fibril formation. FEBS Lett. (0014-5793) 2011 Ferreira N., Saraiva MJ., Almeida MR. suggested by lperfetto ngomes@ibmc.up.pt in vitro In vitro comigration in gel comigration in gel electrophoresis comigration in gel predetermined predetermined participant predetermined Ferreira N., Saraiva MJ., Almeida MR. suggested by lperfetto ngomes@ibmc.up.pt FEBS Lett. (0014-5793) 2011 tthy_human Transthyretin Prealbumin TBPA ATTR TTR PALB protein protein human Homo sapiens Human MASHRLLLLCLAGLVFVSEAGPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE DIP protein P02766 original sequence version: 114 DIP protein P02766 original sequence version: 163 DIP protein P02766 original sequence version: 174 3A6AEBCBBA56BC44 ttr-1 3 TTR 4 weight by comassie molecular weight estimation by coomasie staining weight by comassie predetermined predetermined participant predetermined unspecified role unspecified role neutral component neutral component purified purified Stoichiometry: 4.0 direct interaction direct interaction f1c f1d mint ttr-ttr 2 TTR 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role neutral component neutral component purified purified TTR 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role neutral component neutral component purified purified direct interaction direct interaction homomint mint f2a f4a In accordance with previous results, EGCG powerfully impaired pre-incubated TTR Y78F samples (Fig. 2A, EGCG for 4 and 6 days), thus only soluble protein and small off pathway oligomers, but no large aggregates or fibrils, could be distinguished in the preparations for all time points analysed. Similarly, in curcumin treated samples, only small protein oligomers, but no larger protein aggregates or fibrils (at 4 and 6 days incubation), were detected throughout the period investigated (16 days) (data not shown). In contrast, NDGA pre-incubated samples displayed higher protein aggregation in comparison with samples incubated with other polyphenols, indicating that NDGA was not as effective as curcumin or EGCG in preventing TTR Y78F aggregation (Fig.2A, NDGA at 4 and 6 days).TTR L55P pre-formed fibrils were incubated with the polyphenols for 4 days at 37 ºC. At the end of this incubation period, TEM (Fig. 4A)and DLS (Fig. 4B)analysis evidenced that EGCG, curcumin and NDGA clearly reduced the amount and size of TTR fibrils (dH~5000nm). As expected, EGCG powerfully disrupted TTR pre-formed fibrils into a polydisperse size particle population of small amorphous protein aggregates (Fig. 4). Fibril disruption by curcumin resulted in a major particle population of dH 100nm (Fig. 4B), corresponding to small spherical oligomers (Fig. 4A) while NDGA induced moderate TTR fibril disaggregation as still larger aggregates and fibrils were occasionally observed in NDGA treated samples (Fig. 4A). ttr-ttr-1 1 TTR 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role neutral component neutral component purified purified TTR 4 predetermined predetermined participant predetermined predetermined predetermined participant predetermined unspecified role unspecified role neutral component neutral component purified purified direct interaction direct interaction homomint mint f2b f4b Initially, (0 days) the sample was composed by particles of 8 nm hydrodynamic diameter (dH) (Fig. 2B) which is consistent with previous report for the soluble 7 TTR molecule [17]. After 4 days incubation, the control sample (black line) exhibited a monodisperse particle population of dH around 2000nm, corresponding to large protein aggregates and fibrils. TEM (Fig. 4A)and DLS (Fig. 4B)analysis evidenced that EGCG, curcumin and NDGA clearly reduced the amount and size of TTR fibrils (dH~5000nm). As expected, EGCG powerfully disrupted TTR pre-formed fibrils into a polydisperse size particle population of small amorphous protein aggregates (Fig. 4). Fibril disruption by curcumin resulted in a major particle population of dH 100nm (Fig. 4B), corresponding to small spherical oligomers (Fig. 4A) while NDGA induced moderate TTR fibril disaggregation as still larger aggregates and fibrils were occasionally observed in NDGA treated samples (Fig. 4A).