Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Hereditary fibrinogen amyloidosis is characterized by deposition of amyloid fibrils in renal glomeruli. The subunit protein of the amyloid fibrils is a proteolytic fragment of the fibrinogen Aalpha-chain. ⋯ We have carried out a full structural characterization of amyloid fibrils taken from disease tissue. These studies revealed that ex vivo fibrinogen amyloid fibrils have a cross-beta structure similar to other chemical types of amyloid fibrils.
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The misfolded conformer of the prion protein (PrP) that aggregates into fibrils is believed to be the pathogenic agent in transmissible spongiform encephalopathies. In order to find fibril interfering compounds a screening assay in solution would be the preferred format to approximate more closely to physical conditions and enable the performance of kinetic studies. However, such an assay is hampered by the high irreproducibility because of the stochastic nature of the fibril formation process. ⋯ The assay was validated by comparison of the 50% fibril inhibition levels of peptide huPrP106-126 by six tetracyclic compounds. With this new assay, the fibrillogenic core (GAAAAGAVVG) of peptide huPrP106-126 was determined and for the first time it was possible to test the inhibition potentials of peptide analogues. Also it was found that variants of peptide huPrP106-126 with proline substitutions at positions Ala(115), Ala(120), or Val(122) inhibited the fibril formation of huPrP106-126.