JWX-A1223 attenuates cognitive deficits and tau protein hyperphosphorylation via the Akt/GSK3β pathway in APP/PS1 mice

Abstract

Backgound: Alzheimer’s disease (AD) is a neurodegenerative disorder marked by cognitive decline, affecting memory, thinking, and behaviour. Its neuropathology includes amyloid plaques and neurofibrillary tangles in the brain. Materials: Amyloid plaques consist of misfolded beta-amyloid protein, while tangles are made of hyperphosphorylated tau protein. Method: After treatment with JWX-A1223, the APP/PS1 mice showed significant cognitive improvement in the Morris water maze test. They had shorter escape latency, reduced swimming distance, and longer stay time in the target quadrant, indicating enhanced spatial learning and memory. Results: The treatment with JWX-A1223 also significantly reduced the phosphorylation levels of tau protein at Ser202, Ser396 and Ser404 sites in the cerebral cortex and hippocampus of mice, while increasing the phosphorylation levels at Ser473 site of Akt and Ser9 site of GSK3β. Conslusion: It indicates that by regulating the activity of the Akt/GSK3β pathway, it alleviates the excessive phosphorylation of tau protein and thereby improves cognitive impairment.