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Aggregation of amyloid ?-peptide (A?) into insoluble fibrils is a key pathological event in Alzheimer’s disease (AD). Under certain conditions, Cu(II) exhibits strong inhibitory ef-fect on the Zn(II)-induced aggregation, which occurs significantly even at nearly physiological concentrations of zinc ion in vitro. Cu(II) is considered as a potential factor in the normal brain preventing A? from aggregating. The possible mechanism of the inhibitory effect of Cu(II) is in-vestigated for the first time by molecular modeling method. In the mono-ring mode, the Y10 residue promotes typical quasi-helix conformations of A?. Specially, [Cu-H13(Np)-Y10(OH)] complex forms a local 3.010 helix conformation. In the multi-ring mode, the side chains of Q15 and E11 residues collaborate harmoniously with other chelating ligands producing markedly low energies and quasi-helix conformations. [Cu-3N-Q15(O)-E11(O1)] and [Cu-H13(Np)-Y10(OH)] complex with quasi-helix conformations may prefer soluble forms in solution. In addition, hydro-gen-bond interactions may be the main driving force for A? aggregation. All the results will pro-vide helpful clues for an improved understanding of the role of Cu(II) in the pathogenesis of AD and contribute to the development of an “anti-amyloid” therapeutic strategy.
Aggregation of amyloid -peptide (A?) Into insoluble fibrils is a key pathological event in Alzheimer’s disease (AD). Under certain conditions, Cu (II) exhibits strong inhibitory ef-fect on the Zn (II) Since significantly even at nearly physiological concentrations of zinc ion in vitro. Cu (II) is considered as a potential factor in the normal brain preventing A® from aggregating. The possible mechanism of the inhibitory effect of Cu (II) is in-vestigated for the first time by molecular modeling method. In the mono-ring mode, the Y10 residue promotes typical quasi-helix conformations of A ?. Specially, [Cu-H13 (Np) -Y10 (OH)] complex forms a local 3.010 helix conformation [Cu-3N-Q15 (O) -E11 (O1)] and [Cu -H13 (Np) -Y10 (OH)] complex with quasi-helix conformations may prefer soluble forms in All the results will pro-vide helpful clues for an improved understanding of the role of Cu (II) in the pathogenesis of AD and contribute to the development of an “anti-amyloid” therapeutic strategy.