CuII(atsm) inhibits ferroptosis: Implications for treatment of neurodegenerative disease

Abstract

Background and Purpose: Diacetyl-bis(4-methyl-3-thiosemicarbazonato)copperII (CuII(atsm)) ameliorates neurodegeneration and delays disease progression in mouse models of amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), yet the mechanism of action remains uncertain. Promising results were recently reported for separate Phase 1 studies in ALS patients and PD patients. Affected tissue in these disorders shares features of elevated Fe, low glutathione and increased lipid peroxidation consistent with ferroptosis, a novel form of regulated cell death. We therefore evaluated the ability of CuII(atsm) to inhibit ferroptosis. Experimental Approach: Ferroptosis was induced in neuronal..