Necrostatin-1 ameliorates the pathogenesis of experimental autoimmune encephalomyelitis by suppressing apoptosis and necroptosis of oligodendrocyte precursor cells.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by neuronal demyelination. MS pathogenesis occurs via multiple mechanisms, and is mediated in part by oligodendrocyte apoptosis and a robust inflammatory response. In the present study, Necrostatin-1 (Nec-1), a specific inhibitor of the receptor-interacting protein 1 kinase domain, was revealed to effectively alleviate the severity and pathological damage associated with experimental autoimmune encephalomyelitis (EAE), a commonly used mouse model of MS. In addition, treatment with Nec-1 significantly decreased the number of lesions and inflammatory cell infiltrates in spinal cord tissues, as well as the production of associated pro-inflammatory cytokines, including tumor necrosis factor α (TNFα), interferon-γ and interleukin-1β. Nec-1 also suppressed TNFα + zVAD-fmk-induced apoptosis and necroptosis in primary oligodendrocyte precursor cells. The present study revealed that Nec-1 effectively attenuated the progression of EAE by suppressing apoptosis and necroptosis in oligodendrocytes, and represents a potential novel therapeutic agent for the treatment of MS.