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

By R. Skouta, Scott J. Dixon, Jianlin Wang, Denise E. Dunn, M. Orman, K. Shimada, P. Rosenberg, D. Lo, J. Weinberg, A. Linkermann and 1 more. Journal of the American Chemical Society, 2014

1,009 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Nutrition and Dietetics

View Paper: https://www.semanticscholar.org/paper/12a74ab908bba83792fc8a3da05487966a2bad1d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

In Nutrition and Dietetics

Citations in the corpus

FINO2 Initiates Ferroptosis Through GPX4 Inactivation and Iron Oxidation (2018, neutral): “3, 12 Using an in vitro colorimetric assay, we monitored the oxidation state of iron treated with oxidizing compounds (Figure 5A).”
Neuronal Cell Death. (2018, neutral): “Overexpression of huntingtin exon-1 fragment with an expanded pathogenic polyglutamine repeat (Q73) in corticostriatal brain slices resulted in death of medium spiny neurons by ferroptosis (634).”
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. (2017, positive): “…have been shown to be sensitive to ferroptosis, including hippocampal postnatal rat brain slices treated with glutamate (Dixon et al., 2012), striatal rat brain slices with ectopic mutant huntingtin expression (Skouta et al., 2014), and freshly isolated renal tubules (Linkermann et al., 2014).”
Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications (2021, background): “PUFA oxidation is a critical step in ferroptosis during cellular response to diverse stimuli.(170,243) The oxidation of arachidonoyl (C20:4) fatty acyl chains in the context of PE PLs (i.”
Role of Mitochondria in Ferroptosis (2018, background): “A role of ferroptosis in neurodegeneration has also been implicated (Chen et al., 2015; Do Van et al., 2016; Skouta et al., 2014).”
Imidazole ketone erastin induces ferroptosis and slows tumor growth in a mouse lymphoma model (2019, positive): “The decrease in the phospholipids PC and PE upon IKE treatment is consistent with the effects of piperazine-erastin treatment and erastin treatment on lipid composition in HT-1080 cells (Yang et al., 2016; Skouta et al., 2014).”
GPx4, Lipid Peroxidation, and Cell Death: Discoveries, Rediscoveries, and Open Issues (2017, positive): “Ferrostatin-1 was also identiﬁed as a potent inhibitor of fer-roptosis for which a free radical scavenging mechanism had been proposed (103).”
HSPB1 as a Novel Regulator of Ferroptotic Cancer Cell Death (2015, background): “, excitotoxic cell death, Huntington’s disease, periventricular leukomalacia, and renal injury) (6, 39), as well as the protective role of HSPB1 in these diseases (40), it will be important to elucidate the mechanisms underlying HSPB1-mediated ferroptosis resistance under various conditions.”
NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis (2019, background): “protect against ischemic injury in the brain, liver, kidney, and heart and reduce neurodegenerative phenotypes in a number of cell and animal models, as well as prevent excess iron-induced ferroptosis in cardiomyocytes [56,62,63].”
Synchronized renal tubular cell death involves ferroptosis (2014, methodology): “SRS15-72B was cleared rapidly with a half-life of t1/2 = 2 min (Table S1).”