Research Article-Electrochemical Investigation into the interaction of Fe(II) and Fe(III) with Tau Protein-Potential Implications for Alzheimer’s Disease

Published: 04-05-2020| Version 2 | DOI: 10.17632/bdwcgmvttk.2
Contributors:
Soha Ahmadi,
Iraklii I. Ebralidze,
Zhe She,
Heinz-Bernhard Kraatz

Description

Tau, a family of microtubule-associated protein that exists in six isoforms, is involved in the etiology of Alzheimer’s and upon hypophosphorylation gives rise to neurofibrillary tangles inside neurons. Here, we report the results of an electrochemical investigation into the interaction of Fe(II) and Fe(III) with surface-supported tau (Tau-410, 2N3R). Changes in current density and impedance changes were used to monitor metal-tau interactions and tau-tau interactions. Our detailed electrochemical studies of surface-supported tau protein are supported by X-ray photoelectron spectroscopy and by measurement of interactions in solution by circular dichroism spectroscopy. Also, we include the effects of tau phosphorylation on the interactions with Fe(II) and Fe(III). Our results demonstrate that a) Fe(II) and Fe(III) bind to the tau protein, b) structural changes occur to tau upon metal binding, c) Fe(II) shows a more pronounced effect, d) phosphorylation affects the metal ion complexation and e) tau-tau interactions are mediated by Fe(II). References: (1) Ahmadi, S.; Zhu, S.; Sharma, R.; Wu, B.; Soong, R.; Majumdar, R. D.; Wilson, D. J.; Simpson, A. J.; Kraatz, H.-B. Aggregation of Microtubule Binding Repeats of Tau Protein Is Promoted by Cu2+. ACS Omega 2019, 4 (3), 5356–5366. https://doi.org/10.1021/acsomega.8b03595. (2) Ahmadi, S.; Wu, B.; Song, R.; Zhu, S.; Simpson, A.; Wilson, D. J.; Kraatz, H. B. Exploring the Interactions of Iron and Zinc with the Microtubule Binding Repeats R1 and R4. J. Inorg. Biochem. 2020, 205, 110987. https://doi.org/10.1016/j.jinorgbio.2019.110987. (3) Ahmadi, S.; Zhu, S.; Sharma, R.; Wilson, D. J.; Kraatz, H.-B. Interaction of Metal Ions with Tau Protein. The Case for a Metal-Mediated Tau Aggregation. J. Inorg. Biochem. 2019, 194, 44–51.

Files