Abstract
Background: With the development of society, Neurodegenerative disease (ND), such as alzheimer's disease, is more and more important to the researchers. Metal iron may play a crucial role in this disease, so our research constructed the iron overloading model in nerve cells, induce the ferroptosis, simulate the state of the nerve in the body, and used the anesthesia Dexmedetomidine (Dex), and study whether the Dex can inhibit the ferroptosis and reduce the ND.Methods: Cell proliferation kit CCK8 and PI/Hoechst fluorescence double staining were used to detect the proliferation and apoptosis of HT22 cells. Western blot (WB) was used to detect the expression of PTGS2 and ACSL4, pathway proteins mTOR, TFR1. ROS content in HT22 cells was determined by DHE fluorescence probe. Lipid Peroxidation in nerve cells was detected by MDA Assay. Mito-ferrorange fluorescent probe was used to detect the level of ferrous ions in cells to demonstrate that ferroptosis occurred in nerve cells and Dex could protect nerve cells from ferroptosis.Results: Dex inhibits ferroptosis by regulating the mTOR-TFR1 pathway, reducing lipid peroxidation, intracellular reactive oxygen accumulation (ROS), reducing iron ions, and alleviating mitochondrial damage. mTOR is a well-known autophagy target and has been found to be closely related to ferroptosis. Dex activates the mTOR pathway, inhibits iron entry into the cell, reduces iron influx, and prevents ferroptosis by fenton reaction between excessive iron and lipids in the cell.Conclusion: Dex protects nerve cells from ferroptosis by regulating the mTOR-TFR1 pathway.