Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models

  • J Am Chem Soc. 2014 Mar 26;136(12):4551-6. doi: 10.1021/ja411006a.
Rachid Skouta  1 ,  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
Affiliations
  • 1. Department of Biological Sciences, Columbia University , 550 West 120th Street Northwest Corner Building, MC 4846 New York, New York 10027, United States.
PMID: 24592866 DOI: 10.1021/ja411006a
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.

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