However, previous studies showed that PERK activation in oligodendrocytes promotes their survival in EAE,39, 57 and suggest that ER stress in oligodendrocytes is beneficial in demyelinating diseases.4, 8 In contrast to its beneficial role in oligodendrocyte survival, we found that neuronal intrinsic ER stress is injurious to neurons in EAE, as in ON trauma and glaucoma. Here, EIF2AK3 is linked to demyelinating disease.