Fig. 6.

The metallocomplex Cu^II(atsm) protects against glial ferroptosis and neurotoxic glial activation in vitro. a Chemical structure of Cu^II(atsm). b Cu^II(atsm) prevents RSL3-induced (2 µM) lipid peroxidation in mixed primary cultures of murine microglia and astrocytes, with efficacy similar to the ferroptosis inhibitors liproxstatin-1 (Lip1) and ferrostatin-1 (Fer1). Lipid peroxidation measured as oxidised:reduced C11-BODIPY (n = 2–4). c Cu^II(atsm) mitigates RSL3-induced (25 nM; 8 h) expression of genes associated with ferroptosis in microglial cultures (n = 3–4). d Cu^II(atsm) mitigates ferroptotic stress-induced expression of genes associated with activation of microglia and astrocytes in mixed glial cultures (n = 3–6; RSL3 200 nM; iron as ferric ammonium citrate). e Cu^II(atsm) inhibits RSL3- (100 nM) and erastin-induced generation of neurotoxic glial conditioned medium, resulting in neuroprotection (MTT reduction). Data points in e represent independent cultures. P values (e) indicate significant differences where indicated. Error margins in b, e are S.E.M. Symbols (b) or individual heatmap values (c, d) represent mean