Ferrostatins Inhibit Oxidative Lipid Damage and Cell Death in Diverse Disease Models

نویسندگان

  • 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
چکیده

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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عنوان ژورنال:

دوره 136  شماره 

صفحات  -

تاریخ انتشار 2014