Tuning the rate of aggregation of hIAPP into amyloid using small-molecule modulators of assembly

• Published in: Nature communications Vol. 13; no. 1; pp. 1040 - 15
• Main Authors: Xu, Yong, Maya-Martinez, Roberto, Guthertz, Nicolas, Heath, George R., Manfield, Iain W., Breeze, Alexander L., Sobott, Frank, Foster, Richard, Radford, Sheena E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.02.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 101/6; 631/45; 631/57; 82/58; Agglomeration; Alzheimer's disease; Amylin; Amyloid; Amyloid - metabolism; Amyloidogenesis; Amyloidogenic Proteins - metabolism; Assembly; Binding; Chemical compounds; Chemical kinetics; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Drug development; Elongated structure; Elongation; Fibrils; Fluorescence; Humanities and Social Sciences; Humans; Islet Amyloid Polypeptide - metabolism; Islets of Langerhans - metabolism; Kinetics; Lag phase; Mass spectrometry; Mass spectroscopy; Modulators; Molecular biology; Monomers; multidisciplinary; NMR; Nuclear magnetic resonance; Nucleation; Peptides; Polypeptides; Reaction kinetics; Science; Science (multidisciplinary); Scientific imaging; Titration

Human islet amyloid polypeptide (hIAPP) self-assembles into amyloid fibrils which deposit in pancreatic islets of type 2 diabetes (T2D) patients. Here, we applied chemical kinetics to study the mechanism of amyloid assembly of wild-type hIAPP and its more amyloidogenic natural variant S20G. We show...