Ferroptosis Inhibition: Mechanisms and Opportunities

Jose Pedro Friedmann Angeli, Ron Shah, Derek A. Pratt, Marcus Conrad, Trends in Pharmacological Sciences, Available online 28 March 2017, ISSN 0165-6147, doi:10.1016/j.tips.2017.02.005.

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.

Supplementation of cell media with deuterated linoleic acid (LA) was investigated, and has proven beneficial in several cell models of lipid peroxidation-related neurological disease including PD and Friedreich’s ataxia. In addition,it was also recently shown that cells exposed to deuterated LA presented a marked resistance to ferroptosis.

Ever since therecognition of the privileged position of a-tocopherol as Nature’s premier lipid-soluble Radical-Trapping Antioxidants, researchers have developed with success synthetic compounds with increased reactivity towards peroxyl radicals.


  Ferroptosis Inhibition: Mechanisms and Opportunities