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The human plasma-protein transthyretin (TTR), a well-known amyloid-inhibiting protein, is interestingly also expressed within the IAPP producing \u03b2-cells. In the present study, we have characterized the ability of TTR to interfere with IAPP amyloid-formation, both in terms of its intrinsic stability as well as with regard to the effect of TTR-stabilizing drugs. The results show that TTR can prolong the lag-phase as well as impair elongation in the course of IAPP-amyloid formation. We also show that the interfering ability correlates inversely with the thermodynamic stability of TTR, while no such correlation was observed as a function of kinetic stability. Furthermore, we demonstrate that the ability of TTR to interfere is maintained also at the low pH environment within the IAPP-containing granules of the pancreatic \u03b2-cells. However, at both neutral and low pH, the addition of TTR-stabilizing drugs partly impaired its efficacy. Taken together, these results expose mechanisms of TTR-mediated inhibition of IAPP amyloid-formation and highlights a potential therapeutic target to prevent the onset of T2DM.<\/jats:p>","DOI":"10.3390\/biom11030411","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T13:27:20Z","timestamp":1615382840000},"page":"411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Mechanisms of Transthyretin Inhibition of IAPP Amyloid Formation"],"prefix":"10.3390","volume":"11","author":[{"given":"Sanduni","family":"Wasana Jayaweera","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3430-3101","authenticated-orcid":false,"given":"Solmaz","family":"Surano","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Pettersson","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"Oskarsson","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lovisa","family":"Lettius","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9070-6215","authenticated-orcid":false,"given":"Anna","family":"Gharibyan","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Intissar","family":"Anan","sequence":"additional","affiliation":[{"name":"Wallenberg Centre for Molecular Medicine, Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Olofsson","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Ume\u00e5 University, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1146\/annurev-biochem-061516-045115","article-title":"Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade","volume":"86","author":"Chiti","year":"2017","journal-title":"Annu. Rev. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.1073\/pnas.84.11.3881","article-title":"Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells","volume":"84","author":"Westermark","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8628","DOI":"10.1073\/pnas.84.23.8628","article-title":"Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients","volume":"84","author":"Cooper","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2798269","DOI":"10.1155\/2016\/2798269","article-title":"Islet Amyloid Polypeptide: Structure, Function, and Pathophysiology","volume":"2016","author":"Akter","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/head.13077","article-title":"Amylin","volume":"57","author":"Hay","year":"2017","journal-title":"Headache"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.physbeh.2016.02.034","article-title":"Amylin-mediated control of glycemia, energy balance, and cognition","volume":"162","year":"2016","journal-title":"Physiol. Behav."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1152\/physrev.00042.2009","article-title":"Islet amyloid polypeptide, islet amyloid, and diabetes mellitus","volume":"91","author":"Westermark","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3634","DOI":"10.1172\/JCI69866","article-title":"Human IAPP-induced pancreatic beta cell toxicity and its regulation by autophagy","volume":"124","author":"Shigihara","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_9","first-page":"291","article-title":"The pancreatic islet cells in insular amyloidosis in human diabetic and non-diabetic adults","volume":"81","author":"Westermark","year":"1973","journal-title":"Acta Pathol. Microbiol. Scand. A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/0014-5793(93)81444-5","article-title":"Human islet amyloid polypeptide transgenic mice as a model of non-insulin-dependent diabetes mellitus (NIDDM)","volume":"323","author":"Fox","year":"1993","journal-title":"FEBS Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1007\/BF00400803","article-title":"Chronic overproduction of islet amyloid polypeptide\/amylin in transgenic mice: Lysosomal localization of human islet amyloid polypeptide and lack of marked hyperglycaemia or hyperinsulinaemia","volume":"36","author":"Hoppener","year":"1993","journal-title":"Diabetologia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.2337\/diabetes.53.6.1509","article-title":"Diabetes due to a progressive defect in beta-cell mass in rats transgenic for human islet amyloid polypeptide (HIP Rat): A new model for type 2 diabetes","volume":"53","author":"Butler","year":"2004","journal-title":"Diabetes"},{"key":"ref_13","first-page":"1777","article-title":"The insulin and islet amyloid polypeptide genes contain similar cell-specific promoter elements that bind identical beta-cell nuclear complexes","volume":"12","author":"German","year":"1992","journal-title":"Mol. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4173","DOI":"10.1016\/S0021-9258(19)39539-0","article-title":"Islet amyloid polypeptide. A new beta cell secretory product related to islet amyloid deposits","volume":"265","author":"Nishi","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Gharibyan, A.L., Islam, T., Pettersson, N., Golchin, S.A., Lundgren, J., Johansson, G., Genot, M., Schultz, N., Wennstrom, M., and Olofsson, A. (2020). Apolipoprotein E Interferes with IAPP Aggregation and Protects Pericytes from IAPP-Induced Toxicity. Biomolecules, 10.","DOI":"10.3390\/biom10010134"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16284","DOI":"10.1021\/bi051432v","article-title":"The role of His-18 in amyloid formation by human islet amyloid polypeptide","volume":"44","author":"Abedini","year":"2005","journal-title":"Biochemistry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15598","DOI":"10.1021\/ja205007j","article-title":"Low pH acts as inhibitor of membrane damage induced by human islet amyloid polypeptide","volume":"133","author":"Khemtemourian","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.febslet.2004.09.075","article-title":"Islet amyloid polypeptide-induced membrane leakage involves uptake of lipids by forming amyloid fibers","volume":"577","author":"Sparr","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.bbapap.2015.04.005","article-title":"Dissociation of a BRICHOS trimer into monomers leads to increased inhibitory effect on Abeta42 fibril formation","volume":"1854","author":"Biverstal","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"31608","DOI":"10.1074\/jbc.M112.393157","article-title":"BRICHOS domains efficiently delay fibrillation of amyloid beta-peptide","volume":"287","author":"Willander","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.bbrc.2009.12.122","article-title":"The extracellular domain of Bri2 (ITM2B) binds the ABri peptide (1-23) and amyloid beta-peptide (Abeta1-40): Implications for Bri2 effects on processing of amyloid precursor protein and Abeta aggregation","volume":"393","author":"Peng","year":"2010","journal-title":"BioChem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6958","DOI":"10.1074\/jbc.M115.689539","article-title":"Clusterin Binds to Abeta1-42 Oligomers with High Affinity and Interferes with Peptide Aggregation by Inhibiting Primary and Secondary Nucleation","volume":"291","author":"Beeg","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"18644","DOI":"10.1074\/jbc.272.30.18644","article-title":"Interaction of apolipoprotein J-amyloid beta-peptide complex with low density lipoprotein receptor-related protein-2\/megalin. A mechanism to prevent pathological accumulation of amyloid beta-peptide","volume":"272","author":"Hammad","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/372092a0","article-title":"Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments","volume":"372","author":"Ma","year":"1994","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0304-3940(92)90444-C","article-title":"Apolipoprotein E: A pathological chaperone protein in patients with cerebral and systemic amyloid","volume":"135","author":"Wisniewski","year":"1992","journal-title":"Neurosci. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15181","DOI":"10.1523\/JNEUROSCI.1542-12.2012","article-title":"Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid beta peptide","volume":"32","author":"Hashimoto","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Garai, K., Ghosh, S., Sil, T.B., and Dolai, S. (2018). Apolipoprotein E interacts with amyloid-\u03b2 oligomers via positively cooperative multivalent binding. bioRxiv, 473892.","DOI":"10.1101\/473892"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6323","DOI":"10.1021\/bi5008172","article-title":"The binding of apolipoprotein E to oligomers and fibrils of amyloid-beta alters the kinetics of amyloid aggregation","volume":"53","author":"Garai","year":"2014","journal-title":"Biochemistry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1016\/j.jmb.2019.04.019","article-title":"The Molecular Basis for Apolipoprotein E4 as the Major Risk Factor for Late-Onset Alzheimer\u2019s Disease","volume":"431","author":"Raulin","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/protein\/gzw008","article-title":"Transthyretin variants with improved inhibition of beta-amyloid aggregation","volume":"29","author":"Mangrolia","year":"2016","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19423","DOI":"10.1523\/JNEUROSCI.2561-13.2013","article-title":"Mechanisms of transthyretin inhibition of beta-amyloid aggregation in vitro","volume":"33","author":"Li","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1016\/j.bbadis.2013.09.011","article-title":"Transthyretin suppresses the toxicity of oligomers formed by misfolded proteins in vitro","volume":"1832","author":"Cascella","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4086","DOI":"10.1074\/jbc.271.8.4086","article-title":"Selective inhibition of Abeta fibril formation","volume":"271","author":"Wood","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1016\/j.jmb.2018.06.005","article-title":"Transthyretin Interferes with Abeta Amyloid Formation by Redirecting Oligomeric Nuclei into Non-Amyloid Aggregates","volume":"430","author":"Nilsson","year":"2018","journal-title":"J. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0006-8993(95)00873-O","article-title":"Apolipoproteins E3 and E4 induce, and transthyretin prevents accumulation of the Alzheimer\u2019s beta-amyloid peptide in cultured vascular smooth muscle cells","volume":"698","author":"Frackowiak","year":"1995","journal-title":"Brain Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/j.clinbiochem.2005.08.007","article-title":"Transthyretin inhibition of amyloid beta aggregation and toxicity","volume":"38","author":"Giunta","year":"2005","journal-title":"Clin. BioChem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.febslet.2008.02.034","article-title":"Transthyretin binding to A-Beta peptide--impact on A-Beta fibrillogenesis and toxicity","volume":"582","author":"Costa","year":"2008","journal-title":"FEBS Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12483","DOI":"10.1523\/JNEUROSCI.2417-11.2011","article-title":"Neuronal production of transthyretin in human and murine Alzheimer\u2019s disease: Is it protective?","volume":"31","author":"Li","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.neuroscience.2008.12.045","article-title":"Asymmetric expression patterns of brain transthyretin in normal mice and a transgenic mouse model of Alzheimer\u2019s disease","volume":"159","author":"Tsai","year":"2009","journal-title":"Neuroscience"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7707","DOI":"10.1523\/JNEUROSCI.2211-04.2004","article-title":"Neutralization of transthyretin reverses the neuroprotective effects of secreted amyloid precursor protein (APP) in APPSW mice resulting in tau phosphorylation and loss of hippocampal neurons: Support for the amyloid hypothesis","volume":"24","author":"Stein","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1073\/pnas.0712197105","article-title":"Transthyretin protects Alzheimer\u2019s mice from the behavioral and biochemical effects of Abeta toxicity","volume":"105","author":"Buxbaum","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1002\/cmdc.201800031","article-title":"Transthyretin Mimetics as Anti-beta-Amyloid Agents: A Comparison of Peptide and Protein Approaches","volume":"13","author":"Pate","year":"2018","journal-title":"ChemMedChem"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"429274","DOI":"10.1155\/2008\/429274","article-title":"Transthyretin and amyloid in the islets of Langerhans in type-2 diabetes","volume":"2008","author":"Westermark","year":"2008","journal-title":"Exp. Diabetes Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1006\/jmbi.2000.4078","article-title":"A comparative analysis of 23 structures of the amyloidogenic protein transthyretin","volume":"302","author":"Hornberg","year":"2000","journal-title":"J. Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1210\/jcem-22-6-617","article-title":"An evaluation of the role of prealbumin in the binding of thyroxine","volume":"22","author":"Hollander","year":"1962","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/S0022-2275(20)39396-2","article-title":"Extraction and recombination studies of the interaction of retinol with human plasma retinol-binding protein","volume":"13","author":"Goodman","year":"1972","journal-title":"J. Lipid. Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ciccone, L., Shi, C., di Lorenzo, D., Van Baelen, A.C., and Tonali, N. (2020). The Positive Side of the Alzheimer\u2019s Disease Amyloid Cross-Interactions: The Case of the Abeta 1-42 Peptide with Tau, TTR, CysC, and ApoA1. Molecules, 25.","DOI":"10.3390\/molecules25102439"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"13527","DOI":"10.1021\/bi00041a032","article-title":"Comparison of lethal and nonlethal transthyretin variants and their relationship to amyloid disease","volume":"34","author":"McCutchen","year":"1995","journal-title":"Biochemistry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"15051","DOI":"10.1073\/pnas.93.26.15051","article-title":"Inhibiting transthyretin amyloid fibril formation via protein stabilization","volume":"93","author":"Miroy","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1001\/jama.2013.283815","article-title":"Repurposing diflunisal for familial amyloid polyneuropathy: A randomized clinical trial","volume":"310","author":"Berk","year":"2013","journal-title":"JAMA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1056\/NEJMoa1805689","article-title":"Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy","volume":"379","author":"Maurer","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Iakovleva, I., Begum, A., Brannstrom, K., Wijsekera, A., Nilsson, L., Zhang, J., Andersson, P.L., Sauer-Eriksson, A.E., and Olofsson, A. (2016). Tetrabromobisphenol A Is an Efficient Stabilizer of the Transthyretin Tetramer. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153529"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6507","DOI":"10.1021\/acs.jmedchem.5b00544","article-title":"Enthalpic Forces Correlate with the Selectivity of Transthyretin-Stabilizing Ligands in Human Plasma","volume":"58","author":"Iakovleva","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Eze, F.N., Leelawatwattana, L., and Prapunpoj, P. (2019). Structural Stabilization of Human Transthyretin by Centella asiatica (L.) Urban Extract: Implications for TTR Amyloidosis. Biomolecules, 9.","DOI":"10.3390\/biom9040128"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1042\/bj2040171","article-title":"The internal pH and membrane potential of the insulin-secretory granule","volume":"204","author":"Hutton","year":"1982","journal-title":"BioChem. J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1006\/jsbi.2000.4268","article-title":"Amyloid fibril formation from full-length and fragments of amylin","volume":"130","author":"Goldsbury","year":"2000","journal-title":"J. Struct. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7606","DOI":"10.1039\/C4CP05563B","article-title":"On the lag phase in amyloid fibril formation","volume":"17","author":"Arosio","year":"2015","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9758","DOI":"10.1073\/pnas.1218402110","article-title":"Proliferation of amyloid-beta42 aggregates occurs through a secondary nucleation mechanism","volume":"110","author":"Cohen","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"106511","DOI":"10.1016\/j.bpc.2020.106511","article-title":"Expression, purification and characterisation of large quantities of recombinant human IAPP for mechanistic studies","volume":"269","author":"Lundqvist","year":"2021","journal-title":"Biophys. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"11453","DOI":"10.1021\/bi010673+","article-title":"Anion shielding of electrostatic repulsions in transthyretin modulates stability and amyloidosis: Insight into the chaotrope unfolding dichotomy","volume":"40","author":"Hammarstrom","year":"2001","journal-title":"Biochemistry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11442","DOI":"10.1021\/bi011194d","article-title":"An engineered transthyretin monomer that is nonamyloidogenic, unless it is partially denatured","volume":"40","author":"Jiang","year":"2001","journal-title":"Biochemistry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.cell.2005.01.018","article-title":"The biological and chemical basis for tissue-selective amyloid disease","volume":"121","author":"Sekijima","year":"2005","journal-title":"Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nsmb.2971","article-title":"A molecular chaperone breaks the catalytic cycle that generates toxic Abeta oligomers","volume":"22","author":"Cohen","year":"2015","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1111\/febs.15075","article-title":"Apolipoprotein E impairs amyloid-beta fibril elongation and maturation","volume":"287","author":"Islam","year":"2020","journal-title":"FEBS J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1021\/acs.biomac.9b01475","article-title":"Transthyretin Inhibits Primary and Secondary Nucleations of Amyloid-beta Peptide Aggregation and Reduces the Toxicity of Its Oligomers","volume":"21","author":"Ghadami","year":"2020","journal-title":"Biomacromolecules"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"055102","DOI":"10.1063\/1.4817000","article-title":"Acidic pH retards the fibrillization of human Islet Amyloid Polypeptide due to electrostatic repulsion of histidines","volume":"139","author":"Li","year":"2013","journal-title":"J. Chem. Phys."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/74082","article-title":"Rational design of potent human transthyretin amyloid disease inhibitors","volume":"7","author":"Klabunde","year":"2000","journal-title":"Nat. Struct. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Iakovleva, I., Begum, A., Pokrzywa, M., Walfridsson, M., Sauer-Eriksson, A.E., and Olofsson, A. (2015). The flavonoid luteolin, but not luteolin-7-O-glucoside, prevents a transthyretin mediated toxic response. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128222"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.neulet.2016.02.042","article-title":"Effects of different isoforms of apoE on aggregation of the alpha-synuclein protein implicated in Parkinson\u2019s disease","volume":"618","author":"Emamzadeh","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"32916","DOI":"10.1074\/jbc.271.51.32916","article-title":"Amyloid beta-peptide is transported on lipoproteins and albumin in human plasma","volume":"271","author":"Biere","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"12184","DOI":"10.1073\/pnas.1708805114","article-title":"Inhibition of curli assembly and Escherichia coli biofilm formation by the human systemic amyloid precursor transthyretin","volume":"114","author":"Jain","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1002\/pro.3396","article-title":"Inhibition of amyloid beta fibril formation by monomeric human transthyretin","volume":"27","author":"Garai","year":"2018","journal-title":"Protein Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1021\/bi4001613","article-title":"Transthyretin as both a sensor and a scavenger of beta-amyloid oligomers","volume":"52","author":"Yang","year":"2013","journal-title":"Biochemistry"},{"key":"ref_74","unstructured":"(2021, February 15). Mutations in Hereditary Amyloidosis. Available online: http:\/\/www.amyloidosismutations.com\/mut-attr.php."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S0022-2836(02)00471-0","article-title":"Native state hydrogen exchange study of suppressor and pathogenic variants of transthyretin","volume":"320","author":"Liu","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4421","DOI":"10.1021\/acs.biochem.8b00642","article-title":"NMR Measurements Reveal the Structural Basis of Transthyretin Destabilization by Pathogenic Mutations","volume":"57","author":"Leach","year":"2018","journal-title":"Biochemistry"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.jmb.2013.01.008","article-title":"Localized structural fluctuations promote amyloidogenic conformations in transthyretin","volume":"425","author":"Lim","year":"2013","journal-title":"J. Mol. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1006\/jmbi.2000.4220","article-title":"Search for intermediate structures in transthyretin fibrillogenesis: Soluble tetrameric Tyr78Phe TTR expresses a specific epitope present only in amyloid fibrils","volume":"304","author":"Redondo","year":"2000","journal-title":"J. Mol. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jmb.2012.02.031","article-title":"From macroscopic measurements to microscopic mechanisms of protein aggregation","volume":"421","author":"Cohen","year":"2012","journal-title":"J. Mol. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"9384","DOI":"10.1073\/pnas.1401564111","article-title":"Differences in nucleation behavior underlie the contrasting aggregation kinetics of the Abeta40 and Abeta42 peptides","volume":"111","author":"Meisl","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s12551-017-0289-z","article-title":"Monomer-dependent secondary nucleation in amyloid formation","volume":"9","author":"Linse","year":"2017","journal-title":"Biophys. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Paulsson, J.F., Ludvigsson, J., Carlsson, A., Casas, R., Forsander, G., Ivarsson, S.A., Kockum, I., Lernmark, A., Marcus, C., and Lindblad, B. (2014). High plasma levels of islet amyloid polypeptide in young with new-onset of type 1 diabetes mellitus. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093053"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1021\/bi401164k","article-title":"pH dependence of amylin fibrillization","volume":"53","author":"Jha","year":"2014","journal-title":"Biochemistry"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1111\/j.1742-4658.2009.06936.x","article-title":"Stability and fibril formation properties of human and fish transthyretin, and of the Escherichia coli transthyretin-related protein","volume":"276","author":"Lundberg","year":"2009","journal-title":"FEBS J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S1474-4422(20)30368-9","article-title":"Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study","volume":"20","author":"Adams","year":"2021","journal-title":"Lancet Neurol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/3\/411\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:33:41Z","timestamp":1760160821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/3\/411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,10]]},"references-count":85,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["biom11030411"],"URL":"https:\/\/doi.org\/10.3390\/biom11030411","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,10]]}}}