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Immunoproteasome-dependent neuronal ferroptosis in multiple sclerosis

David C. Rubinsztein^1,2,*

¹Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
²UK Dementia Research Institute, Cambridge Biomedical Campus, Cambridge, UK
* Correspondence: David C. Rubinsztein(dcr1000@cam.ac.uk)

Woo et al. reported in Cell that in multiple sclerosis (MS) mouse models and likely in human MS, a cascade is initiated by neuroinflammation, which leads to a switch in neurons from the conventional proteasome to the immunoproteasome, compromising proteasome activity. This results in elevation of PFKB3, which lowers antioxidant defenses, making neurons more susceptible to ferroptotic cell death.

https://doi.org/10.1038/s41422-025-01162-z

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