Orally administered diflunisal stabilizes transthyretin against dissociation required for amyloidogenesis

References

• Colon W, Kelly J W. Partial denaturation of transthyretin is sufficient for amyloid fibril formation in vitro. Biochemistry 1992; 31: 8654–8660
   PubMed Web of Science ®Google Scholar
• Kelly J W. Alternative conformations of amyloidogenic proteins govern their behavior. Curr Opin Struct Biol 1996; 6: 11–17
   PubMed Web of Science ®Google Scholar
• Kelly J W. Amyloid fibril formation and protein misassembly: a structural quest for insights into amyloid and prion diseases. Structure 1997; 5: 595–600
   PubMed Web of Science ®Google Scholar
• Lai Z H, Colon W, Kelly J W. The acid-mediated denaturation pathway of transthyretin yields a conformational intermediate that can self-assembly into amyloid. Biochemistry 1996; 35: 6470–6482
   PubMed Web of Science ®Google Scholar
• Hammarström P, Schneider F, Kelly J W. Trans-suppression of misfolding in an amyloid disease. Science 2001; 293: 2459–2462
   PubMed Web of Science ®Google Scholar
• Hammarström P, Wiseman R L, Powers E T, Kelly J W. Prevention of transthyretin amyloid disease by changing protein misfolding energetics. Science 2003; 299: 713–716
   PubMed Web of Science ®Google Scholar
• Coelho T, Carvalho M, Saraiva M J, Alves I, Almeida M R, Costa P P. A striking benign evolution of FAP in an individual found to be a compound heterozygote for two TTR mutations: TTR Met 30 and TTR Met 119. J Rheumatol 1993; 20: 179
   Google Scholar
• Miroy G J, Lai Z, Lashuel H A, Peterson S A, Strang C, Kelly J W. Inhibiting transthyretin amyloid fibril formation via protein stabilization. Proc Natl Acad Sci USA 1996; 93: 15051–15056
   PubMed Web of Science ®Google Scholar
• Peterson S A, Klabunde T, Lashuel H A, Purkey H, Sacchettini J C, Kelly J W. Inhibiting transthyretin conformational changes that lead to amyloid fibril formation. Proc Natl Acad Sci USA 1998; 95: 12956–12960
   PubMed Web of Science ®Google Scholar
• Baures P W, Peterson S A, Kelly J W. Discovering transthyretin amyloid fibril inhibitors by limited screening. Bioorg Med Chem 1998; 6: 1389–1401
   PubMed Web of Science ®Google Scholar
• Johnson S M, Wiseman R L, Sekijima Y, Green N S, Adamski-Werner S L, Kelly J W. Native state kinetic stabilization as a strategy to ameliorate protein misfolding diseases: a focus on the transthyretin amyloidoses. Acc Chem Res 2005; 38: 911–921
   PubMed Web of Science ®Google Scholar
• Baures P W, Oza V B, Peterson S A, Kelly J W. Synthesis and evaluation of inhibitors of transthyretin amyloid formation based on the non-steroidal anti-inflammatory drug, flufenamic acid. Bioorg Med Chem 1999; 7: 1339–1347
   PubMed Web of Science ®Google Scholar
• Oza V B, Smith C, Raman P, Koepf E K, Lashuel H A, Petrassi H M, Chiang K P, Powers E T, Sachattinni J, Kelly J W. Synthesis, structure, and activity of diclofenac analogues as transthyretin amyloid fibril formation inhibitors. J Med Chem 2002; 45: 321–332
   PubMed Web of Science ®Google Scholar
• Razavi H, Palaninathan S K, Powers E T, Wiseman R L, Purkey H E, Mohamedmohaideen N N, Deechongkit S, Chiang K P, Dendle M TA, Sacchettinni J C, Kelly J W. Benzoxazoles as transthyretin amyloid fibril inhibitors: synthesis, evaluation, and mechanism of action. Angew Chem Int Ed 2003; 42: 2758–2761
   PubMed Web of Science ®Google Scholar
• Green N S, Palaninathan S K, Sacchettini J C, Kelly J W. Synthesis and characterization of potent bivalent amyloidosis inhibitors that bind prior to transthyretin tetramerization. J Am Chem Soc 2003; 125: 13404–13414
   PubMed Web of Science ®Google Scholar
• Adamski-Werner S L, Palaninathan S K, Sacchettini J C, Kelly J W. Diflunisal analogues stabilize the native state of transthyretin. Potent inhibition of amyloidogenesis. J Med Chem 2004; 47: 355–374
   PubMed Web of Science ®Google Scholar
• Purkey H E, Palaninathan S K, Kent K C, Smith C, Safe S H, Sacchettini J C, Kelly J W. Hydroxylated polychlorinated biphenyls selectively bind transthyretin in blood and inhibit amyloidogenesis: rationalizing rodent PCB toxicity. Chem Biol 2004; 11: 1719–1728
   PubMed Web of Science ®Google Scholar
• Razavi H, Powers E T, Purkey H E, Adamski-Werner S L, Chiang K P, Dendle M T, Kelly J W. Design, synthesis, and evaluation of oxazole transthyretin amyloidogenesis inhibitors. Bioorg Med Chem Lett 2005; 15: 1075–1078
   PubMed Web of Science ®Google Scholar
• Purkey H E, Dorrell M I, Kelly J W. Evaluating the binding selectivity of transthyretin amyloid fibril inhibitors in blood plasma. Proc Natl Acad Sci USA 2001; 98: 5566–5571
   PubMed Web of Science ®Google Scholar
• Miller S R, Sekijima Y, Kelly J W. Native state stabilization by NSAIDs inhibits transthyretin amyloidogenesis from the most common familial disease variants. Lab Invest 2004; 84: 545–552
   PubMed Web of Science ®Google Scholar
• Tempero K F, Cirillo V J, Steelman S L. Diflunisal – review of pharmacokinetic and pharmacodynamic properties, drug interactions, and special tolerability studies in humans. Br J Clin Pharmacol 1977; 4: S31–S36
   Web of Science ®Google Scholar
• Steelman S L, Cirillo V J, Tempero K F. Chemistry, pharmacology and clinical pharmacology of diflunisal. Curr Med Res Opin 1978; 5: 506–514
   PubMed Web of Science ®Google Scholar
• Nuernberg B, Koehler G, Brune K. Pharmacokinetics of diflunisal in patients. Clin Pharmacokinet 1991; 20: 81–89
   PubMed Web of Science ®Google Scholar
• Wiseman R L, Green N S, Kelly J W. Kinetic stabilization of an oligomeric protein under physiological conditions demonstrated by a lack of subunit exchange: implications for transthyretin amyloidosis. Biochemistry 2005; 44: 9265–9274
   PubMed Web of Science ®Google Scholar
• Wiseman R L, Johnson S M, Kelker M S, Foss T, Wilson I A, Kelly J W. Kinetic stabilization of an oligomeric protein by a single ligand binding event. J Am Chem Soc 2005; 127: 5540–5551
   PubMed Web of Science ®Google Scholar
• Foss T R, Kelker M S, Wiseman R L, Wilson I A, Kelly J W. Kinetic stabilization of the native state by protein engineering: implications for inhibition of transthyretin amyloidosis. J Mol Biol 2005; 347: 841–854
   PubMed Web of Science ®Google Scholar
• Umbenhauer E R. Diflunisal in the treatment of the pain of osteoarthritis – summary of clinical studies. Pharmacotherapy 1983; 3: 55–60
   Web of Science ®Google Scholar
• Turner R A, Shackleford R W, Whipple J P. Comparison of diflunisal and aspirin in long-term treatment of patients with rheumatoid-arthritis. Clin Ther 1986; 9: 37–46
   PubMed Web of Science ®Google Scholar
• Hammarström P, Jiang X, Hurshman A R, Powers E T, Kelly J W. Sequence-dependent denaturation energetics: a major determinant in amyloid disease diversity. Proc Natl Acad Sci USA 2002; 99: 16427–16432
   PubMed Web of Science ®Google Scholar
• Lashuel H A, Wurth C, Woo L, Kelly J W. The most pathogenic transthyretin variant, L55P, forms amyloid fibrils under acidic conditions and protofilaments under physiological conditions. Biochemistry 1999; 38: 13560–13573
   PubMed Web of Science ®Google Scholar
• Hurshman A R, White J T, Powers E T, Kelly J W. Transthyretin aggregation under partially denaturing conditions is a downhill polymerization. Biochemistry 2004; 43: 7365–7381
   PubMed Web of Science ®Google Scholar
• Verbeeck R K, Boel A, Buntinx A, Deschepper P J. Plasma-protein binding and interaction studies with diflunisal, a new salicylate analgesic. Biochem Pharmacol 1980; 29: 571–576
   PubMed Web of Science ®Google Scholar
• Honore B, Brodersen R. Albumin binding of anti-inflammatory drugs – utility of a site-oriented versus a stoichiometric analysis. Mol Pharmacol 1984; 25: 137–150
   PubMed Web of Science ®Google Scholar
• Munro S L, Lim C F, Hall J G, Barlow J W, Craik D J, Topliss D J, Stockigt J R. Drug competition for thyroxine binding to transthyretin (prealbumin): comparison with effects on thyroxine-binding globulin. J Clin Endocrinol Metab 1989; 68: 1141–1147
   PubMed Web of Science ®Google Scholar
• Altland K, Winter P, Sauerborn M K. Electrically neutral microheterogeneity of human plasma transthyretin detected by isoelectric focusing in urea gradients. Electrophoresis 1999; 20: 1349–1364
   PubMed Web of Science ®Google Scholar
• Pettersson T M, Carlstrom A, Ehrenberg A, Jornvall H. Transthyretin microheterogeneity and thyroxine binding are influenced by non-amino acid components and glutathione constituents. Biochem Biophys Res Comm 1989; 158: 341–347
   PubMed Web of Science ®Google Scholar
• Suhr O B, Svendsen I H, Ohlsson P I, Lendoire J, Trigo P, Tashima K, Ranlov P J, Ando Y. Impact of age and amyloidosis on thiol conjugation of transthyretin in hereditary amyloidosis. Amyloid 1999; 6: 187–191
   PubMed Web of Science ®Google Scholar
• Kopelman M, Mokady S, Cogan U. Comparative studies of human and chicken retinol-binding proteins and prealbumins. Biochim Biophys Acta 1976; 439: 442–448
   PubMed Web of Science ®Google Scholar
• Lim A, Sengupta S, McComb M E, Theberge R, Wilson W G, Costello C E, Jacobsen D W. In vitro and in vivo interactions of homocysteine with human plasma transthyretin. J Biol Chem 2003; 50: 49707–49713
   Google Scholar
• Connors L H, Lim A, Prokaeva T, Roskens V A, Costello C E. Tabulation of human transthyretin (TTR) variants. Amyloid 2003; 10: 160–184
   PubMed Web of Science ®Google Scholar
• Jacobson D R, Pastore R, Pool S, Malendowicz S, Kane I, Shivji A, Embury S H, Ballas S K, Buxbaum J N. Revised transthyretin Ile 122 allele frequency in African-Americans. Hum Genet 1996; 98: 236–238
   PubMed Web of Science ®Google Scholar
• Jacobson D R, Pastore R D, Yaghoubian R, Kane I, Gallo G, Buck F S, Buxbaum J N. Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans. N Engl J Med 1997; 336: 466–473
   PubMed Web of Science ®Google Scholar
• Sekijima Y, Wiseman L R, Matteson J, Hammarström P, Miller S R, Sawkar A R, Balch W E, Kelly J W. The biological and chemical basis for tissue selective amyloid disease. Cell 2005; 121: 73–85
   PubMed Web of Science ®Google Scholar
• Sekijima Y, Tokuda T, Kametani F, Tanaka K, Maruyama K, Ikeda S. Serum transthyretin monomer in patients with familial amyloid polyneuropathy. Amyloid 2001; 8: 257–262
   PubMed Web of Science ®Google Scholar
• Afolabi I, Hamidi A K, Nakamura M, Jacobs P, Hendrie H, Benson M D. Transthyretin isoleucine-122 mutation in African and American Blacks. Amyloid 2000; 7: 121–125
   PubMed Web of Science ®Google Scholar
• Sekijima Y, Hammarström P, Matsumura M, Shimizu Y, Iwata M, Tokuda T, Ikeda S, Kelly J W. Energetic characteristics of the new transthyretin variant A25T may explain its atypical central nervous system pathology. Lab Invest 2003; 83: 409–417
   PubMed Web of Science ®Google Scholar
• Holmgren G, Ericzon B G, Groth C G, Steen L, Suhr O, Andersen O, Wallin B G, Seymour A, Richardson S, Hawkins P N, Pepys M B. Clinical improvement and amyloid regression after liver-transplantation in hereditary transthyretin amyloidosis. Lancet 1993; 341: 1113–1116
   PubMed Web of Science ®Google Scholar
• Suhr O B, Ericzon B G, Friman S. Long-term follow-up of survival of liver transplant recipients with familial amyloid polyneuropathy (Portuguese type). Liver Transpl 2002; 8: 787–794
   PubMed Web of Science ®Google Scholar
• Dubrey S W, Davidoff R, Skinner M, Bergethon P, Lewis D, Falk R H. Progression of ventricular wall thickening after liver transplantation for familial amyloidosis. Transplantation 1997; 64: 74–80
   PubMed Web of Science ®Google Scholar
• Yazaki M, Tokuda T, Nakamura A, Higashikata T, Koyama J, Higuchi K, Harihara Y, Baba S, Kametani F, Ikeda S. Cardiac amyloid in patients with familial amyloid polyneuropathy consists of abundant wild-type transthyretin. Biochem Biophys Res Commun 2000; 274: 702–706
   PubMed Web of Science ®Google Scholar
• Hammarström P, Sekijima Y, White J T, Wiseman R L, Lim A, Costello C E, Altland K, Garzuly F, Budka H, Kelly J W. D18G transthyretin is monomeric, aggregation prone, and not detectable in plasma and cerebrospinal fluid: a prescription for central nervous system amyloidosis?. Biochemistry 2003; 42: 6656–6663
   PubMed Web of Science ®Google Scholar
• Ando Y, Terazaki H, Nakamura M, Ando E, Haraoka K, Yamashita T, Ueda M, Okabe H, Sasaki Y, Tanihara H, Uchino M, Inomata Y. A different amyloid formation mechanism: de novo oculoleptomeningeal amyloid deposits after liver transplantation. Transplantation 2004; 77: 345–349
   PubMed Web of Science ®Google Scholar
• Cornwell G G, III, Murdoch W L, Kyle R A, Westermark P, Pitkanen P. Frequency and distribution of senile cardiovascular amyloid – a clinicopathologic correlation. Am J Med 1983; 75: 618–623
   PubMed Web of Science ®Google Scholar
• Sousa M M, Cardoso I, Fernandes R, Guimaraes A, Saraiva M J. Deposition of transthyretin in early stages of familial amyloidotic polyneuropathy – evidence for toxicity of nonfibrillar aggregates. Am J Pathol 2001; 159: 1993–2000
   PubMed Web of Science ®Google Scholar
• Sousa M M, Fernandes R, Palha J A, Taboada A, Vieira P, Saraiva M J. Evidence for early cytotoxic aggregates in transgenic mice for human transthyretin Leu55Pro. Am J Pathol 2002; 161: 1935–1948
   PubMed Web of Science ®Google Scholar
• Reixach N, Deechongkit S, Jiang X, Kelly J W, Buxbaum J N. Tissue damage in the amyloidoses: transthyretin monomers and nonnative oligomers are the major cytotoxic species in tissue culture. Proc Natl Acad Sci USA 2004; 101: 2817–2822
   PubMed Web of Science ®Google Scholar
• Dickson P W, Howlett G J, Schreiber G. Metabolism of prealbumin in rats and changes induced by acute inflammation. Eur J Biochem 1982; 129: 289–293
   PubMedGoogle Scholar
• Ando Y, Tanaka Y, Nakazato M, Ericzon B G, Yamashita T, Tashima K, Sakashita N, Suga M, Uchino M, Ando M. Change in variant transthyretin levels in patients with familial amyloidotic polyneuropathy type I following liver transplantation. Biochem Biophys Res Commun 1995; 211: 354–358
   PubMed Web of Science ®Google Scholar
• Almeida M R, Macedo B, Cardoso I, Alves I, Valencia G, Arsequell G, Planas A, Saraiva M J. Selective binding to transthyretin and tetramer stabilization in serum from patients with familial amyloidotic polyneuropathy by an iodinated diflunisal derivative. Biochem J 2004; 381: 351–356
   PubMed Web of Science ®Google Scholar
• Tagoe C E, Jacobson D R, Gallo G, Buxbaum J N. Mice transgenic for human TTR have the same frequency of renal TTR deposition whether maintained in conventional or specific pathogen free environments. Amyloid 2003; 10: 262–266
   PubMed Web of Science ®Google Scholar
• Teng M H, Yin J Y, Vidal R, Ghiso J, Kumar A, Rabenou R, Shah A, Jacobson D R, Tagoe C, Gallo G, Buxbaum J N. Amyloid and nonfibrillar deposits in mice transgenic for wild-type human transthyretin: a possible model for senile systemic amyloidosis. Lab Invest 2001; 81: 385–396
   PubMed Web of Science ®Google Scholar
• Sousa M M, Fernandes R, Palha J A, Taboada A, Vieira P, Saraiva M J. Evidence for early cytotoxic aggregates in transgenic mice for human transthyretin Leu55Pro. Am J Pathol 2002; 161: 1935–1948
   PubMed Web of Science ®Google Scholar
• Takaoka Y, Ohta M, Miyakawa K, Nakamura O, Suzuki M, Takahashi K, Yamamura K, Sakaki Y. Cysteine 10 is a key residue in amyloidogenesis of human transthyretin Val30Met. Am J Pathol 2004; 164: 337–345
   PubMed Web of Science ®Google Scholar