Proteome Profiling of Experimental Autoimmune Encephalomyelitis\nMouse Model and the Effect of a SUMO E1 Inhibitor

Multiple\nsclerosis (MS) is one of the most common neurodegenerative\ndiseases, causing demyelination and inflammation in the central nervous\nsystem. The pathology of MS has been extensively studied using the\nexperimental autoimmune encephalomyelitis (EAE) mouse model. However,\nthe molecular mechanisms are still largely unclear and require further\ninvestigation. In this study, we carried out quantitative proteomic\nanalysis of the brain and spinal cord tissues in mice induced with\nEAE using a data-independent acquisition strategy and identified 744\ndifferentially regulated proteins in the brain and 741 in the spinal\ncord. The changed proteins were highly related with phagocytosis,\nlysosomal enzymes, inflammasome activation, complements, and synaptic\nloss processes. Moreover, gene set enrichment analysis revealed the\nelevation of the SUMOylation process in EAE with the increase of SUMOylation-related\nenzymes and modification targets. Furthermore, to test the possibility\nof treating MS by targeting SUMOylation, we explored the application\nof a selective SUMO E1 inhibitor, TAK-981. Intriguingly, TAK-981 suppressed\nthe global SUMOylation level in the brain and significantly alleviated\nthe symptoms of EAE in mice. Our findings contribute to a better understanding\nof MS pathology, reveal the important role of SUMOylation in disease\nprogression, and demonstrate the potential of the SUMO E1 inhibitor\nas a novel treatment for MS.