Interferon-induced immunoproteasomes disturb neuronal metabolism and drive neurodegeneration in multiple sclerosis [RNS_Seq3_Nuclei]

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. Here, we analyzed the mRNA expression of neurons during acute EAE 15 days after active immunization. We isolated the neuronal nuclei by flow cytometry sorting from the spinal cords of the mice. Thereby, we can seperate non-neuronal NeuN negative from neuronal NeuN positive nuclei.