title: Disaggregation ability of different chelating molecules on copper ion-triggered amyloid fibers.
abstract: Dysfunctional interaction of amyloid-β (Aβ) with excess metal ions is proved to be related to the etiology of Alzheimer's disease (AD). Using metal-binding compounds to reverse metal-triggered Aβ aggregation has become one of the potential therapies for AD. In this study, the ability of a carboxylic acid gemini surfactant (SDUC), a widely used metal chelator (EDTA), and an antifungal drug clioquinol (CQ) in reversing the Cu(2+)-triggered Aβ(1-40) fibers have been systematically studied by using turbidity essay, BCA essay, atomic force microscopy, transmission electron microscopy, and isothermal titration microcalorimetry. The results show that the binding affinity of Cu(2+) with CQ, SDUC, and EDTA is in the order of CQ > EDTA > SDUC, while the disaggregation ability to Cu(2+)-triggered Aβ(1-40) fibers is in the order of CQ > SDUC > EDTA. Therefore, the disaggregation ability of chelators to the Aβ(1-40) fibers does not only depend on the binding affinity of the chelators with Cu(2+). Strong self-assembly ability of SDUC and π-π interaction of the conjugate group of CQ also contributes toward the disaggregation of the Cu(2+)-triggered Aβ(1-40) fibers and result in the formation of mixed small aggregates.
authors: Key Laboratory of Colloid and Interface Science, Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences , Beijing 100190, P. R. China.
authors: Linyi
authors: L
authors: Zhu
authors: Yuchun
authors: Y
authors: Han
authors: Chengqian
authors: C
authors: He
authors: Xu
authors: X
authors: Huang
authors: Yilin
authors: Y
authors: Wang
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002151:Calorimetry; D002614:Chelating Agents / Q000737:chemistry*; D007464:Clioquinol / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D007477:Ions / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D007477:Ions; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D003300:Copper; D007464:Clioquinol