| Endoplasmic reticulum (ER) stress is a cellular homeostatic mechanism, which is utilized by cells to adapt to inter- and intra-cellular changes. There is a burgeoning literature showing that the human endogenous retroviral envelope glycoprotein, Syncyin-1, oxidative stress and reactive oxygen species (ROS) participate in the pathogenesis of multiple sclerosis (MS). I investigated the contribution of Syncytin-1-induced ER stress in MS and its animal model, experiment autoimmune encephalomyelitis (EAE). The prototypic ER stress biomarker, XBP-1 spliced variant (XBP-1/S), was increased in cerebral white matter of MS patients compared to non-MS controls and was correlated with Syncytin-1 expression. Syncytin-1 over-expression caused glia cytotoxicity but was mitigated by the ROS scavenger, crocin. Treatment with crocin on day 7 post-EAE induction ameliorated EAE disease severity in mice by reducing EAE pathology. Herein, I demonstrate that crocin attenuates Syncytin-1-induced ER stress in astrocytes while also diminishing disease severity in EAE in conjunction with suppression of neuroinflammation. |
