NF-kappa B, a potential therapeutic target for the treatment of multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) that afflicts over 2 million people worldwide. On the basis of the temporal course of disease, MS can be subdivided into three clinical groups: relapsing remitting MS (RR-MS), secondary progressive MS and primary progressive MS. There is a high degree of clinical diversity within these subgroups. The pathogenesis of MS in most patients is likely to result from autoreactive, activated CD4(+) T cells moving from the periphery across the blood brain barrier into the CNS. Most therapeutic agents used in MS (e.g. immunosuppressive and immunomodulatory drugs and cell cycle interruption drugs) are only used for RR-MS. These treatments show some efficiency in lessening the relapse rate in RR-MS and time to progression, but cannot cure MS. Thus, there is a need for new efficient treatments for all types of MS. An increasing number of studies indicate that nuclear factor-kappaB plays an important role in controlling expression of genes relevant to the pathogenesis of autoimmunity. Genetic factors related to NF-kappaB may also be determinants of MS susceptibility, as polymorphisms in the molecules involved in regulation of the NF-kappaB signal transduction pathway differ between RR-MS and progressive MS. Herein, the role of NF-kappaB in MS will be reviewed and its potential as a new therapeutic target in MS will be considered and compared with existing treatments.