Identification and Validation of the Nrf2/Slc2a1 Axis in Alzheimer's Disease.

Background/Objects: Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive cognitive decline. Although Nrf2 is a key regulator of oxidative stress in AD, the molecular factors associated with Nrf2 signaling and their potential regulatory relationships remain incompletely understood. This study aimed to systematically identify and validate a novel Nrf2-associated signaling axis in AD. Results: Slc2a1 was identified as a key Nrf2-associated candidate gene. In the SCOP-induced AD model, reduced Nrf2 expression was accompanied by decreased Slc2a1 expression, cognitive impairment, hippocampal neuronal injury, excessive ROS accumulation, and mitochondrial abnormalities. Pharmacological modulation of Nrf2 was associated with corresponding changes in Slc2a1 expression, while Nrf2 activation was accompanied by improvements in oxidative stress and neuronal injury. Conclusions: This study identifies a potential functional relationship between Nrf2 signaling and Slc2a1 expression in AD-related pathology and proposes the Nrf2/Slc2a1 pathway as a potential mechanistic framework linking oxidative stress to mitochondrial abnormalities.