TY - JOUR TI - An arylthiazyne derivative is a potent inhibitor of lipid peroxidation and ferroptosis providing neuroprotection in vitro and in vivo AU - Keuters, Meike Hedwig AU - Keksa-Goldsteine, Velta AU - Dhungana, Hiramani AU - Huuskonen, Mikko T. AU - Pomeshchik, Yuriy AU - Savchenko, Ekaterina AU - Korhonen, Paula K. AU - Singh, Yajuvinder AU - Wojciechowski, Sara AU - Lehtonen, Šárka AU - Kanninen, Katja M. AU - Malm, Tarja AU - Sirviö, Jouni AU - Muona, Anu AU - Koistinaho, Milla AU - Goldsteins, Gundars AU - Koistinaho, Jari T2 - Scientific Reports AB - Lipid peroxidation-initiated ferroptosis is an iron-dependent mechanism of programmed cell death taking place in neurological diseases. Here we show that a condensed benzo[b]thiazine derivative small molecule with an arylthiazine backbone (ADA-409-052) inhibits tert-Butyl hydroperoxide (TBHP)-induced lipid peroxidation (LP) and protects against ferroptotic cell death triggered by glutathione (GSH) depletion or glutathione peroxidase 4 (GPx4) inhibition in neuronal cell lines. In addition, ADA-409-052 suppresses pro-inflammatory activation of BV2 microglia and protects N2a neuronal cells from cell death induced by pro-inflammatory RAW 264.7 macrophages. Moreover, ADA-409-052 efficiently reduces infarct volume, edema and expression of pro-inflammatory genes in a mouse model of thromboembolic stroke. Targeting ferroptosis may be a promising therapeutic strategy in neurological diseases involving severe neuronal death and neuroinflammation. DA - 2021/02/10/ PY - 2021 DO - 10.1038/s41598-021-81741-3 DP - www.nature.com VL - 11 IS - 1 SP - 3518 LA - en SN - 2045-2322 UR - https://www.nature.com/articles/s41598-021-81741-3 Y2 - 2021/02/10/17:58:36 ER -