Endoplasmic reticulum (ER) stress is a 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 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.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/1387 |
| Date | 11 1900 |
| Creators | Deslauriers, Andre |
| Contributors | Power, Christopher (Medicine, Medical Microbiology and Immunology), Guilbert, Larry (Medical Microbiology and Immunology), Michalak, Marek (Biochemistry), Giulinani, Fabrizio (Medicine) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 3360693 bytes, application/pdf |
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