Nuclear factor kappa B (NF-κB) in multiple sclerosis pathology

• NF-κB signaling in MS patients and animal models of MS.
• NF-κB signaling controls peripheral immune activation at multiple levels.
• NF-κB controls inflammatory responses locally in the CNS.
• NF-κB as a therapeutic target for the treatment of MS.

The nuclear factor kappa B (NF-κB) signaling cascade plays a critical role in the regulation of immune and inflammatory responses and has been implicated in the pathogenesis of autoimmune demyelinating diseases such as multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the main animal model of MS. NF-κB is essential for peripheral immune cell activation and the induction of pathology, but also plays crucial roles in resident cells of the central nervous system (CNS) during disease development. Here we review recent evidence clarifying the role of NF-κB in the different cell compartments contributing to MS pathology and its implications for the development of therapeutic strategies for the treatment of MS and other demyelinating pathologies of the CNS.