Hydrogen-rich water attenuates amyloid β-induced cytotoxicity through upregulation of Sirt1-FoxO3a by stimulation of AMP-activated protein kinase in SK-N-MC cells.

Abstract

Amyloid beta (Aβ) peptides, implicated in Alzheimer's disease pathogenesis, promote reactive oxygen species (ROS) accumulation that leads to mitochondrial dysfunction and apoptotic cell death. Using SK-N-MC neuronal cells, this study examined how hydrogen-rich water (HRW) counteracts Aβ-induced cytotoxicity. HRW was found to directly neutralize excess ROS, thereby reducing oxidative damage. Additionally, HRW activated AMP-activated protein kinase (AMPK), which in turn upregulated forkhead box protein O3a (FoxO3a) through a sirtuin 1 (Sirt1)-dependent mechanism. This signaling cascade suppressed Aβ-induced mitochondrial membrane potential loss and attenuated overall oxidative stress. These findings identify the AMPK–Sirt1–FoxO3a axis as a key pathway through which HRW exerts neuroprotective effects against Aβ toxicity.

Mechanism

HRW activates AMPK, which upregulates FoxO3a via a Sirt1-dependent pathway, scavenging excess ROS and preventing Aβ-induced mitochondrial membrane potential loss and apoptotic cell death.