Mechanisms related to the pathogenesis of the optic neuritis and the development of new therapeutic avenues

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Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), was used in our study to elucidate the possible mechanisms underlying the pathogenesis of the optic neuritis. Firstly, we investigated the effect of apoptosis-related kinase 1 (ASK1) deficiency on the severity of EAE. Our results show that ASK1 deficiency attenuates neuroinflammation in EAE, without affecting the proliferation capability of T cells. Moreover, oral treatment with a specific small molecular weight inhibitor of ASK1 suppressed EAE-induced autoimmune inflammation in both spinal cords and optic nerves. These results suggest that ASK1 may serve as a valid therapeutic target for autoimmune demyelinating disorders including MS. Secondly, we found that the deficiency of olig1, a gene important for the development of oligodendrocytes, delayed the onset of EAE disease, suggesting that the olig1 signaling pathways may be involved in the incidence rate and the severity of neurological symptoms in MS. Thirdly, we found that oral administration of spermidine, a natural component of our diet, reduced the severity of the optic neuritis, suggesting that spermidine might be suitable for the treatment of MS and optic neuritis.