Oxidative stress induces tau hyperphosphorylation via MARK activation in neuroblastoma N1E-115 cells

Yuhong Liu; Yunxi Chen; Koji Fukui

doi:10.3164/jcbn.22-39

Oxidative stress induces tau hyperphosphorylation via MARK activation in neuroblastoma N1E-115 cells

J Clin Biochem Nutr. 2023 Jul;73(1):24-33. doi: 10.3164/jcbn.22-39. Epub 2023 May 16.

Authors

Yuhong Liu¹, Yunxi Chen², Koji Fukui^{1

2}

Affiliations

¹ Molecular Cell Biology Laboratory, Department of Functional Control Systems, Graduate School of Engineering and Science, Shibaura Institute of Technology, Fukasaku 307, Minuma-ku, Saitama 337-8570, Japan.
² Molecular Cell Biology Laboratory, Department of Systems Engineering and Science, School of Engineering and Science, Shibaura Institute of Technology, Fukasaku 307, Minuma-ku, Saitama 337-8570, Japan.

Abstract

Reactive oxygen species are considered a cause of neuronal cell death in Alzheimer's disease (AD). Abnormal tau phosphorylation is a proven pathological hallmark of AD. Microtubule affinity-regulating kinases (MARKs) regulate tau-microtubule binding and play a crucial role in neuronal survival. In this study, we hypothesized that oxidative stress increases the phosphorylation of Ser262 of tau protein through activation of MARKs, which is the main reason for the development of AD. We investigated the relationship between tau hyperphosphorylation on Ser262 and MARKs in N1E-115 cells subjected to oxidative stress by exposure to a low concentration of hydrogen peroxide. This work builds on the observation that hyperphosphorylation of tau is significantly increased by oxidative stress. MARKs activation correlated with tau hyperphosphorylation at Ser262, a site that is essential to maintain microtubule stability and is the initial phosphorylation site in AD. These results indicated that MARKs inhibitors might serve a role as therapeutic tools for the treatment of AD.

Keywords: Alzheimer’s disease; microtubule affinity-regulating kinases; microtubule-associated proteins; oxidative stress; tau phosphorylation.