Interferon-induced immunoproteasomes disturb neuronal metabolism and drive neurodegeneration in multiple sclerosis [RNA_Seq1_Proteasome]

In this study, we investigated the proteasome composition and activity of neurons in CNS inflammation. Therefore, we investigated the multiple sclerosis mouse model and IFNy treated neurons. Thereby, we identified that the immunoproteasome leads to proteasomal dysfunction in neurons with subsequent accumulation of proteins that lead to ferroptosis. Overall design: Here, we analyzed neurons that overexpress a mScarlet control or the proteasomel subunits PSMB5 or PSMB8. Overexpression was achieved by lentiviral transduction at 7 d.i.v, the cells were harvested after an additional 10 d.i.v.