CNS & Neurological Disorders - Drug Targets

(Formerly Current Drug Targets - CNS & Neurological Disorders)

Stephen D. Skaper  
Department of Pharmaceutical and Pharmacological Sciences
University of Padova


Two Nitrogen-containing Ligands as Inhibitors of Metal-Induced Amyloid β-Peptide Aggregation

Author(s): Tingting Chen, Shajun Zhu, Siyuan Liu, Yapeng Lu and Li Zhu

Affiliation: School of Chemistry and Chemical Engineering, Nantong University, 9 Seyuan Rd, Nantong 226019, P. R. China.


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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Article Details

Page: [166 - 172]
Pages: 7
DOI: 10.2174/18715273113129990076