Journal article
Microglial ferroptotic stress causes non-cell autonomous neuronal death
Jeffrey R Liddell, James BW Hilton, Kai Kysenius, Jessica L Billings, Sara Nikseresht, Lachlan E Mcinnes, Dominic J Hare, Bence Paul, Stephen W Mercer, Abdel A Belaidi, Scott Ayton, Blaine R Roberts, Joseph S Beckman, Catriona A McLean, Anthony R White, Paul S Donnelly, Ashley I Bush, Peter J Crouch
Molecular Neurodegeneration | BMC | Published : 2024
Abstract
Background: Ferroptosis is a form of regulated cell death characterised by lipid peroxidation as the terminal endpoint and a requirement for iron. Although it protects against cancer and infection, ferroptosis is also implicated in causing neuronal death in degenerative diseases of the central nervous system (CNS). The precise role for ferroptosis in causing neuronal death is yet to be fully resolved. Methods: To elucidate the role of ferroptosis in neuronal death we utilised co-culture and conditioned medium transfer experiments involving microglia, astrocytes and neurones. We ratified clinical significance of our cell culture findings via assessment of human CNS tissue from cases of the fa..
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Funding Acknowledgements
Human tissue samples were obtained from the Victorian Brain Bank (Florey Institute of Neuroscience and Mental Health, the University of Melbourne, Australia), the MS Society Tissue Bank (Wolfson Neuroscience Laboratories, Imperial College London, United Kingdom), MRC London Neurodegenerative Diseases Brain Bank (King's College, London, UK), the University of Maryland Brain and Tissue Bank, a biorepository of the NIH NeuroBioBank (Maryland, USA), and the Sydney Brain Bank. Dr Antonella Roveri (University of Padova, Italy) provided invaluable advice on measuring GPX4 activity in tissue extracts. All live cell imaging was conducted at the University of Melbourne Biological Optical Microscopy Platform with expert advice from Dr Ellie Hyun-Jung Cho. Histological assessment of human spinal cord was performed at the Histology and Neuropathology Facility (Florey Institute of Neuroscience and Mental Health, the University of Melbourne, Australia) by Dr Ian Birchall. Images in Figure 2, Supplementary Figures 2 & 4, and Graphical Abstract were produced using Biorender.