The role of copper(ii) in the aggregation of human amylin

• DOI: 10.1039/c4mt00130c
• Publication Date: 2014-07-24T10:01:24Z
• Authors: Alessandro Sinopoli; Antonio Magrì; Danilo Milardi; Matteo Pappalardo; Pietro Pucci; Angela Flagiello; Jeremy J. Titman; Vincenzo Giuseppe...; Giuseppe Caruso; Giuseppe Pappalardo; Giuseppe Grasso
• Keywords: Amylin

Amylin is a 37-residue peptide hormone produced by the islet β-cells of pancreas and formation amylin aggregates strongly associated with β-cell degeneration in type 2 diabetes, as demonstrated more than 95% patients exhibiting amyloid upon autopsy. It widely recognized that metal ions such copper(II) have been implicated aggregation process amyloidogenic peptides Aβ α-synuclein there evidence self-assembly also largely affected copper(II). For this reason, work, role has investigated several different experimental approaches. Mass spectrometric investigations show induces significant changes structure, which decrease protein fibrillogenesis observed ThT measurements. Accordingly, solid-state NMR experiments together computational analysis carried out on model fragment confirmed non-fibrillogenic nature induced aggregated structure. Finally, presence shown to major influence proneness be degraded proteases cytotoxicity studies cell cultures are reported.