NF-κB Pathways in the Pathogenesis of Multiple Sclerosis and the Therapeutic Implications

被引:89
作者
Leibowitz, Saskia M. [1 ]
Yan, Jun [1 ]
机构
[1] Univ Queensland, UQ Ctr Clin Res, Brisbane, Qld, Australia
关键词
NF-kappa B; multiple sclerosis; I kappa B-alpha; IKK; signaling pathway; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EPSTEIN-BARR-VIRUS; PLACEBO-CONTROLLED PHASE-3; DENDRITIC CELL MATURATION; IL-1 RECEPTOR ANTAGONIST; ANTIGEN-PRESENTING CELLS; SIGNAL-REGULATED KINASE; TH17; IMMUNE-RESPONSE; AUTOREACTIVE T-CELLS; GM-CSF PRODUCTION;
D O I
10.3389/fnmol.2016.00084
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) signaling pathways are involved in cell immune responses, apoptosis and infections. In multiple sclerosis (MS), NF-kappa B pathways are changed, leading to increased levels of NF-?B activation in cells. This may indicate a key role for NF-kappa B in MS pathogenesis. NF-kappa B signaling is complex, with many elements involved in its activation and regulation. Interestingly, current MS treatments are found to be directly or indirectly linked to NF-kappa B pathways and act to adjust the innate and adaptive immune system in patients. In this review, we will first focus on the intricacies of NF-kappa B signaling, including the activating pathways and regulatory elements. Next, we will theorize about the role of NF-kappa B in MS pathogenesis, based on current research findings, and discuss some of the associated therapeutic implications. Lastly, we will review four new MS treatments which interrupt NF-kappa B pathways-fingolimod, teriflunomide, dimethyl fumarate (DMF) and laquinimod (LAQ)-and explain their mechanisms, and the possible strategy for MS treatments in the future.
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页数:23
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