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Glutathione peroxidase 4: a new player in neurodegeneration?

Abstract

Glutathione peroxidase 4 (GPx4) is an antioxidant enzyme reported as an inhibitor of ferroptosis, a recently discovered non-apoptotic form of cell death. This pathway was initially described in cancer cells and has since been identified in hippocampal and renal cells. In this Perspective, we propose that inhibition of ferroptosis by GPx4 provides protective mechanisms against neurodegeneration. In addition, we suggest that selenium deficiency enhances susceptibility to ferroptotic processes, as well as other programmed cell death pathways due to a reduction in GPx4 activity. We review recent studies of GPx4 with an emphasis on neuronal protection, and discuss the relevance of selenium levels on its enzymatic activity.

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Acknowledgements

BRC is supported by a Science without Borders (Ciência sem Fronteiras) Fellowship. DJH and BRR receive financial support from the Australian Research Council Linkage Projects scheme (LP140100095). We wish to acknowledge support from the Victorian Government Operational Infrastructure Support Program, and the Cooperative Research Centre for Mental Health.

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Correspondence to B R Cardoso or B R Roberts.

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Cardoso, B., Hare, D., Bush, A. et al. Glutathione peroxidase 4: a new player in neurodegeneration?. Mol Psychiatry 22, 328–335 (2017). https://doi.org/10.1038/mp.2016.196

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