Magnesium-L-threonate exhibited a neuroprotective effect against oxidative stress damage in HT22 cells and Alzheimer’s disease mouse model

ARTICLE HIGHLIGHTS

Research background

The increasing prevalence of Alzheimer’s disease (AD) in the elderly population has posed a huge financial and medical burden on the society. Effective methods to block the progression of the cognitive deterioration in AD patients are urgently required. As oxidative stress accounts for a pivotal role in the pathological mechanism of neurodegenerative diseases, including AD, anti-oxidative stress treatments may provide a promising therapeutic direction. Recent study had explored the anti-malondialdehyde effect of magnesium in vitro, however the potential anti-oxidative stress damage effect of Magnesium-L-threonate (MgT) still remains to be verified.

Research motivation

This research investigated the suppressive effect of MgT against oxidative stress injury, thus developing a therapeutic reference basis for the future explorations.

Research objectives

This research aimed to determine the neuroprotective effect of MgT against oxidative stress damage and explore the related mechanism which may bring a research foundation for the feasibility of MgT.

Research methods

As the cell and animal models, amyloid β (Aβ)_25-35-treated HT22 cells and APPswe/PS1dE9 (APP/PS1) mice were treated with MgT administration. After the MgT administration, cell counting kit-8 detection was applied to analysis the viability of HT22 cells and the Morris Water Maze test was used to record the cognition of APP/PS1 mice. Reactive oxygen species (ROS) production of HT22 cells and cell apoptosis of both models were all quantified by using the flow cytometry assay. The expression of hypoxia-inducible factor (HIF)-1α, NADPH oxidase (NOX) 4, Aβ_1-42, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway proteins was quantified by Western blotting.

Research results

MgT effectively suppressed the HT22 cellular injury triggered by Aβ_25-35-induced oxidative stress by elevating the viability, blocking the ROS formation and downregulating HIF-1α. MgT significantly ameliorated the impaired cognitive performance of APP/PS1 mouse and inhibited the upregulation of Aβ_1-42, NOX4 and HIF-1α protein expression. In addition, MgT obviously suppressed the cell apoptosis, regulated apoptotic-related proteins and upregulated the PI3K/Akt pathway in both models. In future research, further explorations are required to confirm the above-mentioned effects of MgT in more disease models.

Research conclusions

This study demonstrates the protective effect of MgT against oxidative stress injury in Aβ_25-35-treated HT22 cells and APP/PS1 mice.

Research perspectives

This study provides a promising therapeutic agent to ameliorate the oxidative stress damage-associated neurodegenerative diseases. More investigations to demonstrate this effect of MgT on other types of Alzheimer’s disease, in vivo models of other neurodegenerative diseases and clinical experiments are required in further research.