University of Cambridge > Talks.cam > Biophysical Seminars > Kinetic Insights into amyloid-β metal ion interactions and implications for AD.

Kinetic Insights into amyloid-β metal ion interactions and implications for AD.

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The kinetics of the interactions between amyloid-β (Aβ) and metal ions are crucial to understanding the physiological and pathological roles of Aβ in the normal brain and in Alzheimer’s disease. Using the quenching of a fluorescent probe by Cu(II), we have elucidated the kinetic mechanism of Aβ/Cu(II) interactions in physiologically relevant conditions. FAD mutations and phosphorylation of Aβ were found to modulate the kinetics of interconversion between the two Cu(II) coordination modes and enhance copper-bridged dimer formation. Further computational reaction-diffusion simulations of the interactions of synaptically released metal ions with Aβ indicated that up to a third of Aβ is Cu(II)-bound under repetitive metal ion release, while any other Aβ-metal complexes (including Aβ-Zn) are insignificant. In addition, the timescale of redox cycling of the Aβ-Cu complex were determined and found biologically relevant. These results suggest that targeting specific interactions between Cu(II) and Aβ may be a viable option in drug development efforts for early stages of AD.

This talk is part of the Biophysical Seminars series.

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