Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models.
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.
Skouta, R; Dixon, SJ; Wang, J; Dunn, DE; Orman, M; Shimada, K; Rosenberg, PA; Lo, DC; Weinberg, JM; Linkermann, A; Stockwell, BR
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