title: Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Columbia University , 550 West 120th Street Northwest Corner Building, MC 4846 New York, New York 10027, United States.
authors.forename: Rachid
authors.initials: R
authors.lastname: Skouta
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Dixon
authors.forename: Jianlin
authors.initials: J
authors.lastname: Wang
authors.forename: Denise E
authors.initials: DE
authors.lastname: Dunn
authors.forename: Marina
authors.initials: M
authors.lastname: Orman
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shimada
authors.forename: Paul A
authors.initials: PA
authors.lastname: Rosenberg
authors.forename: Donald C
authors.initials: DC
authors.lastname: Lo
authors.forename: Joel M
authors.initials: JM
authors.lastname: Weinberg
authors.forename: Andreas
authors.initials: A
authors.lastname: Linkermann
authors.forename: Brent R
authors.initials: BR
authors.lastname: Stockwell
mesh_terms: D016923:Cell Death / Q000187:drug effects; D003514:Cyclohexylamines / Q000494:pharmacology* / Q000627:therapeutic use; D006816:Huntington Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007969:Leukomalacia, Periventricular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010655:Phenylenediamines / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D003514:Cyclohexylamines; D008563:Membrane Lipids; D010655:Phenylenediamines; C573944:ferrostatin-1