Fig. 1
From: Neuronal immunoproteasome and PFKFB3-forced glycolysis: key players in multiple sclerosis
Role of PSMB8 and PFKB3 in neuroinflammation-induced neurodegeneration in multiple sclerosis. Upper: PSMB8 and PFKFB3 are upregulated in neurons of both postmortem MS gray matter and EAE mice. Middle: PSMB8 transcriptional induction by IFNγ in neurons favors the formation of the immunoproteasome, which correlates with increased PFKFB3 levels. Accumulation of PFKFB3 breaks the balance between glycolysis and PPP in detriment of the latter (dotted lines), leading to reduced NADPH synthesis and thus decreased GSH reconstitution. This creates a pro-oxidant environment, which ultimately leads to ferroptosis. Lower: Psmb8 or Pfkfb3 neuronal knock out models improve neuronal pathology in EAE. Some elements of the figure were generated from BioRender
