NF-kappaB inhibition as a therapeutic objective in multiple sclerosis treatment

NF-kB inhibition might be an ideal treatment for multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disorder of the central nervous system (CNS) of unknown cause.

We do not know its cause, and we have yet to identify an ideal treatment, but what we do know is:

  • NF-kB is a central player in the activation of T cells, B cells, dendritic cells, macrophages, and CNS resident glia – all of which are believed to be important in MS disease progression.
  • NF-kB is induced by a large number of extracellular signals and its activation results in both increased production of pro-inflammatory cytokines and increased production of antibody by B cells.
  • IL-17 is probably a key player in MS as well as other autoimmune conditions, and it is a potent activator of NF-kB.
  • Activation of NF-kB in microglial cells and astrocytes of MS patients is known to result in the production of proinflammatory cytokines and potentially neurotoxic mediators.
  • Some drugs currently used in the treatment of MS, such as beta-interferon, are thought to act primarily via inhibition of NF-kB.
  • Curcumin, a major constituent of turmeric, has recently been shown to be effective in the treatment of a wide variety of diseases, including cancer, infection, and autoimmune disease. Curcumin inhibits production of IL-17, and appears to act by inhibiting NF-kB.
  • Many MS patients have a reduced frequency of relapses during pregnancy, due at least in part to altered levels of estrogens. Studies suggest that estrogens inhibit NF-kB, leading to reduced T cell transmigration into the CNS in MS patients and reduced cytokine production.

Taken together, these findings suggest the potential therapeutic benefit of NF-kB inhibition.

The publication:

December, 2008

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

Summary of the abstract

Multiple sclerosis is a chronic inflammatory autoimmune disease of the central nervous system that afflicts over 2 million people worldwide.

The pathogenesis of multiple sclerosis in most patients is likely to result from autoreactive, activated T cells that somehow migrate from the peripheral bloodstream to the central nervous system. Normally, the blood-brain barrier would prevent the movement of these white blood cells into the central nervous system.

Most treatments for multiple sclerosis are intended to reduce inflammation. These treatments show some efficacy in reducing the rate of relapse and increasing the time between relapses. Nonetheless, there is a need for substantially better treatments for multiple sclerosis.

An increasing number of studies indicate that nuclear factor-kappaB (NF-kB) plays an important role in controlling inflammation, by controlling the expression of genes that play a key role in autoimmunity.


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