Two Nitrogen-containing Ligands as Inhibitors of Metal-Induced Amyloid β-Peptide Aggregation
Abnormal interactions of Zn2+ and Cu2+ with the amyloid β-peptide (Aβ) are proposed to play an important
role in the neuropathogenesis of Alzheimer’s disease (AD). Metal chelators are potential therapeutic agents for AD
because they could sequester metals ions from Aβ aggregates and reverse the aggregation. In this study, two nitrogencontaining
ligands, TACN and BPA, have been investigated as possible metal chelators in the therapy of Alzheimer’s
disease. The interactions between the chelators and Aβ40 aggregates are studied by turbidometry, thioflavin T (ThT)
fluorescence spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS), BCA protein assay, circular
dichroism spectroscopy (CD), and atomic force microscopy (AFM). The results demonstrates that TACN and BPA are
capable of both disrupting and preventing Zn2+ or Cu2+-induced Aβ40 aggregation. Moreover, they can also suppress the
production of H2O2 induced by Cu-Aβ40, associated with toxic oxidative stress in AD.
Keywords: Alzheimer’s disease, Amyloid β-peptide, Metal, Chelators.
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