title: Ferroptosis Inhibition: Mechanisms and Opportunities.
abstract: The past decade has yielded tremendous insights into how cells die. This has come with our understanding that several distinct forms of cell death are encompassed under the umbrella term necrosis. Among these distinct forms of regulated necrotic cell death, ferroptosis has attracted considerable attention owing to its putative involvement in diverse pathophysiological processes. A key feature of the ferroptosis process is the requirement of phospholipid peroxidation, a process that has been linked with several human pathologies. Now with the establishment of a connection between lipid peroxidation and a distinctive cell death pathway, the search for new small molecules able to suppress lipid peroxidation has gained momentum and may yield novel cytoprotective strategies. We review here advances in our understanding of the ferroptotic process and summarize the development of lipid peroxidation inhibitors with the ultimate goal of suppressing ferroptosis-relevant cell death and related pathologies.
authors.affiliation: Helmholtz Zentrum München, Institute of Developmental Genetics, 85764 Neuherberg, Germany. Electronic address: pedro.angeli@helmholtz-muenchen.de.
authors.forename: Jose Pedro Friedmann
authors.initials: JPF
authors.lastname: Angeli
authors.affiliation: Department of Chemistry and Biomolecular Sciences University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
authors.forename: Ron
authors.initials: R
authors.lastname: Shah
authors.affiliation: Department of Chemistry and Biomolecular Sciences University of Ottawa, Ottawa, Ontario K1N 6N5, Canada. Electronic address: dpratt@uottawa.ca.
authors.forename: Derek A
authors.initials: DA
authors.lastname: Pratt
authors.affiliation: Helmholtz Zentrum München, Institute of Developmental Genetics, 85764 Neuherberg, Germany. Electronic address: marcus.conrad@helmholtz-muenchen.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Conrad
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D005227:Fatty Acids / Q000494:pharmacology*; D006801:Humans; D007501:Iron / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects*
chemical_list: D005227:Fatty Acids; C013584:lipid peroxidation inhibitor; D007501:Iron
keywords: cell death; cysteine metabolism; glutathione peroxidase; lipid peroxidation; regulated necrosis; small molecules