Esketamine induces tripartite motif-containing protein 24 to improve cognitive dysfunction in Alzheimer's disease.
Neuroscience letters June 21, 2024 Yingbing Tu, Bin Xu 3 citations
Esketamine improved spatial learning and memory in triple transgenic Alzheimer's disease (3xTg-AD) mice. The drug increased expression of TRIM24, which activated the PI3K/AKT pathway in the hippocampus. Depleting TRIM24 reversed these cognitive benefits and blocked PI3K/AKT signaling. Esketamine also reduced neuroinflammation—lowering pro-inflammatory molecules, GFAP, and p-Tau—but this effect was lost when TRIM24 was knocked down. Blocking the PI3K/AKT pathway worsened cognitive deficits and inflammation. Thus, esketamine may counteract Alzheimer's-related cognitive decline by suppressing neuroinflammation through the TRIM24/PI3K/AKT axis.