Prolonging the integrated stress response enhances CNS remyelination in an inflammatory environment

The inflammatory environment of demyelinated lesions in multiple sclerosis (MS) patients contributes to remyelination failure. Inflammation activates a cytoprotective pathway, the integrated stress response (ISR), but it remains unclear whether enhancing ISR can improve an environment. To examine this possibility, stage experimental autoimmune encephalomyelitis (EAE), as well mouse model that incorporates cuprizone-induced demyelination along with CNS delivery proinflammatory cytokine IFN-γ were used here. We demonstrate either genetic or pharmacological enhancement significantly increased number remyelinating oligodendrocytes and remyelinated axons lesions. Moreover, combined treatment modulator Sephin1 oligodendrocyte differentiation reagent bazedoxifene myelin thickness pre-lesion levels. Taken together, our findings indicate prolonging protects promotes presence inflammation, suggesting may provide reparative benefit MS patients.