Ferroptosis Inhibition: Mechanisms and Opportunities

被引:451
作者
Angeli, Jose Pedro Friedmann [1 ]
Shah, Ron [2 ]
Pratt, Derek A. [2 ]
Conrad, Marcus [1 ]
机构
[1] Helmholtz Zentrum Munchen, Inst Dev Genet, D-85764 Neuherberg, Germany
[2] Univ Ottawa, Dept Chem & Biomol Sci, Ottawa, ON K1N 6N5, Canada
基金
加拿大自然科学与工程研究理事会; 加拿大创新基金会;
关键词
GLUTATHIONE-PEROXIDASE; 4; POLYUNSATURATED FATTY-ACIDS; CHAIN-BREAKING ANTIOXIDANTS; NONAPOPTOTIC CELL-DEATH; VITAMIN-E; PARKINSONS-DISEASE; OXIDATIVE STRESS; HUNTINGTONS-DISEASE; MOUSE MODEL; ALOX15; GENE;
D O I
10.1016/j.tips.2017.02.005
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:489 / 498
页数:10
相关论文
共 61 条
[1]   'Mitochondrial energy imbalance and lipid peroxidation cause cell death in Friedreich's ataxia' [J].
Abeti, R. ;
Parkinson, M. H. ;
Hargreaves, I. P. ;
Angelova, P. R. ;
Sandi, C. ;
Pook, M. A. ;
Giunti, P. ;
Abramov, A. Y. .
CELL DEATH & DISEASE, 2016, 7 :e2237-e2237
[2]   Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice [J].
Angeli, Jose Pedro Friedmann ;
Schneider, Manuela ;
Proneth, Bettina ;
Tyurina, Yulia Y. ;
Tyurin, Vladimir A. ;
Hammond, Victoria J. ;
Herbach, Nadja ;
Aichler, Michaela ;
Walch, Axel ;
Eggenhofer, Elke ;
Basavarajappa, Devaraj ;
Radmark, Olof ;
Kobayashi, Sho ;
Seibt, Tobias ;
Beck, Heike ;
Neff, Frauke ;
Esposito, Irene ;
Wanke, Ruediger ;
Foerster, Heidi ;
Yefremova, Olena ;
Heinrichmeyer, Marc ;
Bornkamm, Georg W. ;
Geissler, Edward K. ;
Thomas, Stephen B. ;
Stockwell, Brent R. ;
O'Donnell, Valerie B. ;
Kagan, Valerian E. ;
Schick, Joel A. ;
Conrad, Marcus .
NATURE CELL BIOLOGY, 2014, 16 (12) :1180-U120
[3]   Polyunsaturated fatty acids and their metabolites in brain function and disease [J].
Bazinet, Richard P. ;
Laye, Sophie .
NATURE REVIEWS NEUROSCIENCE, 2014, 15 (12) :771-785
[4]   Vitamin E:: function and metabolism [J].
Brigelius-Flohé, R ;
Traber, MG .
FASEB JOURNAL, 1999, 13 (10) :1145-1155
[5]   Male Subfertility Induced by Heterozygous Expression of Catalytically Inactive Glutathione Peroxidase 4 Is Rescued in Vivo by Systemic Inactivation of the Alox15 Gene [J].
Bruetsch, Simone Hanna ;
Rademacher, Marlena ;
Roth, Sophia Regina ;
Mueller, Karin ;
Eder, Susanne ;
Viertel, Dagmar ;
Franz, Christiane ;
Kuhn, Hartmut ;
Borchert, Astrid .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2016, 291 (45) :23578-23588
[6]   Expression of Inactive Glutathione Peroxidase 4 Leads to Embryonic Lethality, and Inactivation of the Alox15 Gene Does Not Rescue Such Knock-In Mice [J].
Bruetsch, Simone Hanna ;
Wang, Chi Chiu ;
Li, Lu ;
Stender, Hannelore ;
Neziroglu, Nilguen ;
Richter, Constanze ;
Kuhn, Hartmut ;
Borchert, Astrid .
ANTIOXIDANTS & REDOX SIGNALING, 2015, 22 (04) :281-293
[7]  
BURTON GW, 1986, ACCOUNTS CHEM RES, V19, P194, DOI 10.1021/ar00127a001
[8]   Glutathione peroxidase 4: a new player in neurodegeneration? [J].
Cardoso, B. R. ;
Hare, D. J. ;
Bush, A. I. ;
Roberts, B. R. .
MOLECULAR PSYCHIATRY, 2017, 22 (03) :328-335
[9]   Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration [J].
Carlson, Bradley A. ;
Tobe, Ryuta ;
Yefremova, Elena ;
Tsuji, Petra A. ;
Hoffmann, Victoria J. ;
Schweizer, Ulrich ;
Gladyshev, Vadim N. ;
Hatfield, Dolph L. ;
Conrad, Marcus .
REDOX BIOLOGY, 2016, 9 :22-31
[10]   Ablation of the Ferroptosis Inhibitor Glutathione Peroxidase 4 in Neurons Results in Rapid Motor Neuron Degeneration and Paralysis [J].
Chen, Liuji ;
Hambright, William Sealy ;
Na, Ren ;
Ran, Qitao .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290 (47) :28097-28106