Raloxifene Prevents Chemically-Induced Ferroptotic Neuronal Death In Vitro and In Vivo.

ABSTRACT: Ferroptosis, a regulated form of cell death characterized by excessive iron-dependent lipid peroxidation, can be readily induced in cultured cells by chemicals such as erastin and RSL3. Protein disulfide isomerase (PDI) has been identified as an upstream mediator of chemically induced ferroptosis and also a target for ferroptosis protection. In this study, we discovered that raloxifene (RAL), a selective estrogen receptor modulator known for its neuroprotective actions in humans, can effectively inhibit PDI function and provide robust protection against chemically induced ferroptosis in cultured HT22 neuronal cells. Specifically, RAL can bind directly to PDI both in vitro and in intact neuronal cells and inhibit its catalytic activity. Computational modeling analysis reveals that RAL can t

SUBMITTER: Hao X 

PROVIDER: S-EPMC11790820 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature