Whilst our results clearly indicate a role for increased TNF levels in neurodegeneration in MS, it is important to note that there are other triggers for RIPK3/MLKL dependent necroptotic cell death [15, 59, 65], including FasL, TRAIL, dsRNA and viral DNA, although their role in neuronal death has yet to be investigated. Here, MLKL is linked to myeloid sarcoma.