{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T04:39:22Z","timestamp":1774327162314,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[1997,12,12]],"date-time":"1997-12-12T00:00:00Z","timestamp":881884800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["FEBS Letters"],"published-print":{"date-parts":[[1997,12]]},"abstract":"<jats:p>Amyloid fibril formation and deposition are the basis for a wide range of diseases, including spongiform encephalopathies, Alzheimer's and familial amyloidotic polyneuropathies. However, the molecular mechanisms of amyloid formation are still poorly characterised. In certain forms of familial amyloidotic polyneuropathy (FAP), the amyloid fibrils are mostly constituted by variants of transthyretin (TTR). V30M\u2010TTR is the most frequent variant, and L55P\u2010TTR is the variant associated with the most aggressive form of amyloidosis. Here, we report gel filtration chromatography experiments to characterise the aggregation states of WT\u2010, V30M\u2010, L55P\u2010TTR and a non\u2010amyloidogenic variant, T119M\u2010TTR, in solution, at nearly physiological pH. These studies show that all four protein tetramers dissociate to monomer upon dilution, in the sub\u2010micromolar range, at pH 7.0. The amyloidogenic proteins V30M\u2010 and L55P\u2010TTR show a complex equilibrium between monomers, tetramers and high molecular weight aggregate species. These aggregates dissociate directly to monomer upon dilution. This study shows that the tendency to form aggregates among the four studied proteins correlates with their known amyloidogenic potential. Thus, the amyloidogenic mutations could perturb the structure and\/or stability of the monomeric species leading initially to the formation of soluble aggregates and at a later stage to insoluble amyloid fibrils.<\/jats:p>","DOI":"10.1016\/s0014-5793(97)01398-7","type":"journal-article","created":{"date-parts":[[2002,7,25]],"date-time":"2002-07-25T17:53:27Z","timestamp":1027619607000},"page":"297-300","source":"Crossref","is-referenced-by-count":90,"title":["The amyloidogenic potential of transthyretin variants correlates with their tendency to aggregate in solution"],"prefix":"10.1002","volume":"418","author":[{"given":"Alexandre","family":"Quintas","sequence":"first","affiliation":[]},{"given":"M.J.M","family":"Saraiva","sequence":"additional","affiliation":[]},{"given":"Rui M.M","family":"Brito","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[1997,12,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/75.3.408"},{"key":"e_1_2_6_3_1","first-page":"179","volume":"1","author":"Saraiva M.J.M.","year":"1996","journal-title":"J. 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