(American Chemical
Society, 2014) Skouta, Rachid; Dixon, Scott
J.; Wang, Jianlin; Dunn, Denise E.; Orman, Marina; Shimada, Kenichi; Rosenberg, Paul; Lo, Donald C.; Weinberg, Joel M.; Linkermann, Andreas; Stockwell, Brent R.
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.
