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Ferrostatins Inhibit Oxidative Lipid Damage and Cell Death in Diverse Disease Models

2014; American Chemical Society; Volume: 136; Issue: 12 Linguagem: Inglês

10.1021/ja411006a

1943-2984

Rachid Skouta, Scott J. Dixon, Jianlin Wang, Denise E. Dunn, Marina Orman, Kaoru Shimada, Paul A. Rosenberg, Donald C. Lo, Joel M. Weinberg, Andreas Linkermann, Brent R. Stockwell,

Trace Elements in Health

Ferrostatin-1 (Fer-1) inhibits ferroptosis, a form of regulated, oxidative, nonapoptotic cell death. We found that Fer-1 inhibited cell death in cellular models of Huntington's disease (HD), periventricular leukomalacia (PVL), and kidney dysfunction; Fer-1 inhibited lipid peroxidation, but not mitochondrial reactive oxygen species formation or lysosomal membrane permeability. We developed a mechanistic model to explain the activity of Fer-1, which guided the development of ferrostatins with improved properties. These studies suggest numerous therapeutic uses for ferrostatins, and that lipid peroxidation mediates diverse disease phenotypes.