Ferrostatins Inhibit Oxidative Lipid Damage and Cell Death in Diverse Disease Models
journal contributionposted on 17.12.2015, 01:15 by Rachid Skouta, Scott J. Dixon, Jianlin Wang, Denise E. Dunn, Marina Orman, Kenichi Shimada, Paul A. Rosenberg, Donald C. Lo, Joel M. Weinberg, Andreas Linkermann, Brent R. Stockwell
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.