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10.1038/ncomms10787 http://scihub22266oqcxt.onion/10.1038/ncomms10787 C4766415!4766415!26902880     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Commun 2016 ; 7 (ä): ä Nephropedia Template TP {{tp|p=26902880|t=2016. Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity |pdf=|usr=}}{{26902880}} gab.com Text Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=26902880 #FOAvip Transthyretin (TTR) is a plasma homotetrameric protein implicated in fatal systemic amyloidoses. TTR tetramer dissociation precedes pathological TTR aggregation. Native state stabilizers are promising drugs to treat TTR amyloidoses. Here we repurpose tolcapone, an FDA-approved molecule for Parkinson's disease, as a potent TTR aggregation inhibitor. Tolcapone binds specifically to TTR in human plasma, stabilizes the native tetramer in vivo in mice and humans and inhibits TTR cytotoxicity. Crystal structures of tolcapone bound to wild-type TTR and to the V122I cardiomyopathy-associated variant show that it docks better into the TTR T4 pocket than tafamidis, so far the only drug on the market to treat TTR amyloidoses. These data indicate that tolcapone, already in clinical trials for familial amyloid polyneuropathy, is a strong candidate for therapeutic intervention in these diseases, including those affecting the central nervous system, for which no small-molecule therapy exists. Twit Text FOAVip Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=26902880 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26902880 #FOAvip English Wikipedia <ref>{{Cite pmid|26902880}}</ref> Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity #MMPMID26902880 Sant'Anna R; Gallego P; Robinson LZ; Pereira-Henriques A; Ferreira N; Pinheiro F; Esperante S; Pallares I; Huertas O; Rosário Almeida M; Reixach N; Insa R; Velazquez-Campoy A; Reverter D; Reig N; Ventura S Nat Commun 2016[]; 7 (ä): ä PMID26902880show ga Transthyretin (TTR) is a plasma homotetrameric protein implicated in fatal systemic amyloidoses. TTR tetramer dissociation precedes pathological TTR aggregation. Native state stabilizers are promising drugs to treat TTR amyloidoses. Here we repurpose tolcapone, an FDA-approved molecule for Parkinson's disease, as a potent TTR aggregation inhibitor. Tolcapone binds specifically to TTR in human plasma, stabilizes the native tetramer in vivo in mice and humans and inhibits TTR cytotoxicity. Crystal structures of tolcapone bound to wild-type TTR and to the V122I cardiomyopathy-associated variant show that it docks better into the TTR T4 pocket than tafamidis, so far the only drug on the market to treat TTR amyloidoses. These data indicate that tolcapone, already in clinical trials for familial amyloid polyneuropathy, is a strong candidate for therapeutic intervention in these diseases, including those affecting the central nervous system, for which no small-molecule therapy exists. äRepositioning tolcapone as a potent inhibitor of transthyretin amyloid(epmc).pdf DeepDyve Pubget Overpricing