Notch-1 suppressed vascular dementia via modulating AMPK/mTOR/TFEB/YAP signaling induced ferroptosis

The aim of this study is to clarify the molecular mechanism by which Notch-1 prevents vascular dementia (VD) by preventing ferroptosis caused by the AMPK/mTOR/TFEB/YAP pathway. Thirty male SD rats were used in the in vivo tests. They were split into three groups at random: the sham group, the model group, and the model + Notch1-OE group. The water maze test was used to evaluate the rats’ spatial learning and memory capacities. Western blotting was done to look at protein expression in hippocampus tissues, and Nissl staining was utilized to see changes in Nissl bodies. Purchased hippocampus cells were used in in vitro tests, and they were split up into six groups and exposed to various stimuli. Fe2+ levels were assessed, protein expression was observed using Western blotting, and hippocampus cell death was detected using flow cytometry. In vivo, rats with VD treated with Notch1-OE demonstrated enhanced spatial learning and memory, reduced neuronal damage, elevated Nissl bodies, increased expression of the SLC7A11 protein, and significantly decreased expression of the NCOA4 protein. According to in vitro studies, Notch-1 reduced Fe2 + levels, prevented ferroptosis, and decreased apoptosis of hippocampus cells by suppressing P-AMPK and nuclear TFEB protein expression and increasing p-mTOR and nuclear YAP protein production. This, in turn, prevented the development of VD. By modifying the AMPK/mTOR/TFEB/YAP signaling pathway, Notch-1 inhibits VD and controls ferroptosis.