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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.

SUBMITTER: Skouta R

PROVIDER: S-EPMC3985476 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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

Skouta Rachid R Dixon Scott J SJ Wang Jianlin J Dunn Denise E DE Orman Marina M Shimada Kenichi K Rosenberg Paul A PA Lo Donald C DC Weinberg Joel M JM Linkermann Andreas A Stockwell Brent R BR

Journal of the American Chemical Society 20140314 12

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 impr ...[more]

PMID: 24592866

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