Abstract
Ferroptosis is a type of cell death process defined by iron-dependent peroxidation of phospholipids leading to the destruction of cellular membranes and death of the cell. Ferroptosis occurs throughout the body, but a considerable research focus on ferroptosis in the brain — neuroferroptosis — has been driven by the rich lipid and iron content of the brain as well as its high oxygen consumption. Neurons also have an exceptionally large surface area and metabolic demand, which necessitates specific mechanisms (such as lipid antioxidants) to engage constantly to protect the plasma membrane against lipid peroxidation. Ferroptosis has been extensively linked to neurodegeneration and ischaemia and is increasingly implicated in physiological processes such as neuronal reprogramming. Astrocytes provide metabolic support to neurons, enabling them to defend against ferroptosis, yet ferroptotic signals in microglia can propagate damage to astrocytes and neurons, highlighting the complex intercellular (patho)physiology of neuroferroptosis.
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Acknowledgements
This research was funded in whole or part by the Noncommunicable Chronic Diseases — National Science and Technology Major Project (2023ZD0507200) and the National Health and Medical Research Council (GNT2008359). The Florey Institute of Neuroscience and Mental Health acknowledges support from the Victorian Government, in particular funding from the Operational Infrastructure Support Grant. For the purposes of open access, the authors have applied a CC BY public copyright licence to any author accepted manuscript version arising from this submission.
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Lei, P., Walker, T. & Ayton, S. Neuroferroptosis in health and diseases. Nat. Rev. Neurosci. 26, 497–511 (2025). https://doi.org/10.1038/s41583-025-00930-5
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DOI: https://doi.org/10.1038/s41583-025-00930-5
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