Abstract
Amyloid β (Aβ) fibrils and amorphous aggregates are found in the brain of patients with Alzheimer’s disease (AD), and are implicated in the etiology of AD. The metal imbalance is also among leading causes of AD, owing to the fact that Aβ aggregation takes place in the synaptic cleft where Aβ, Cu(II) and Fe(III) are found in abnormally high concentrations. Aβ40 and Aβ42 are the main components of plaques found in afflicted brains. Coordination of Cu(II) and Fe(III) ions to Aβ peptides have been linked to Aβ aggregation and production of reactive oxygen species, two key events in the development of AD pathology. Metal chelation was proposed as a therapy for AD on the basis that it might prevent Aβ aggregation. In this work, we first examined the formation of Aβ40 and Aβ42 aggregates in the presence of metal ions, i.e. Fe(III) and Cu(II), which were detected by fluorescence spectroscopy and atomic force microscopy. Second, we studied the ability of the two chelators, ethylenediaminetetraacetic acid and 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol), to investigate their effect on the availability of these metal ions to interact with Aβ and thereby their effect on Aβ accumulation. Our findings show that Fe(III), but not Cu(II), promote aggregation of both Aβ40 and Aβ42. We also found that only clioquinol decreased significantly iron ion-induced aggregation of Aβ42. The presence of ions and/or chelators also affected the morphology of Aβ aggregates.
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Acknowledgements
We acknowledge the support of the research council of the Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran, without which this work could not be possible to start and finish. We also thank the Department of Chemistry at IASBS for their generous cooperation in providing us the opportunity to make use of their fluorescence spectroscopy facility. Also, we thank the Department of Physics at IASBS for their kind permission to use their AFM facility.
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Tahmasebinia, F., Emadi, S. Effect of metal chelators on the aggregation of beta-amyloid peptides in the presence of copper and iron. Biometals 30, 285–293 (2017). https://doi.org/10.1007/s10534-017-0005-2
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DOI: https://doi.org/10.1007/s10534-017-0005-2