Ferrostatins Inhibit Oxidative Lipid Damage and Cell Death in Diverse Disease Models
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- 作者：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
- 刊名：Journal of the American Chemical Society
- 出版年：2014
- 出版时间：March 26, 2014
- 年：2014
- 卷：136
- 期：12
- 页码：4551-4556
- 全文大小：359K
- 年卷期：v.136,no.12(March 26, 2014)
- ISSN：1520-5126
文摘
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鈥檚 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.