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. Author manuscript; available in PMC: 2024 Dec 1.
Published in final edited form as: Ann Neurol. 2023 Sep 14;94(6):1048–1066. doi: 10.1002/ana.26770

Fig. 7.

Fig. 7.

Summary of data supporting a role for ferroptosis in microglial degeneration in human WMI related to vascular dementia or AD. Injury to myelin promotes the accumulation of myelin debris and lipid uptake by senescent reactive microglia (MG). Disturbances in multiple molecules and genes (brown text) appear to contribute to pronounced oxidative stress that leads to a pronounced increase in the number of DM. Central factors appear to involve dysregulation of iron metabolism, impaired generation of glutathione anti-oxidants and mitochondrial metabolic stress, which together contribute to lipid peroxidation injury and DNA damage. Abbreviations: AKR1C1, Aldo-keto reductase family 1 member C1; DM, degenerative microglia; FTL, Ferritin light chain; FTH, Ferritin heavy chain; FTMT, Ferritin mitochondrial; GPX4, Glutathione peroxidase 4; GCLC, Glutamate-cysteine ligase catalytic subunit; GCLM, Glutamate-cysteine ligase modifier subunit; GSH, reduced glutathione; GSSG, oxidized glutathione; 4-HNE, 4-hydxoynonenol; HMOX1, Heme oxygenase 1; H2A.X, phospho-histone H2A.X; LD, lipid droplets; MG, microglia; PLIN2, perilipin 2; ROS, reactive oxygen species; Tom 20, translocase of outer membrane 20.