Voltage-Gated Sodium Channel Gating Modifiers: Valuable Targets for Multiple Sclerosis Treatment
Enhancement of the sodium current or facilitation of action-potential propagation can retrieve the leakage of sodium current in the demyelinated region. We propose voltage-gated sodium channel (VGSC) gating modifiers as a novel strategy for multiple sclerosis symptom treatment.
Since different VGSC toxins are available, we can change the VGSC function in an arbitrary way. Some well-recognized VGSC modifiers can shift the voltage dependence of the activation gate to more hyperpolarized potentials and inhibit the channel inactivation gate. On the other hand, some VGSCs stabilize the open state of the channel. For example, Alpha-scorpion toxin, sea anemone toxins, and some spider toxins postpone sodium channel inactivation. Experimental data show that the effect of these toxins facilitates the stimulation of VGSC and can increase the flow of sodium during each action potential.3,4
The most important point in using these toxins is that they target specific molecules. They are able to find and interact with their own target, usually at low concentrations. This property is very useful for drug candidates because of the reduction of side effects. There are different types of VGSCs in different neurons. This helps us to target specific channels in relevant neurons using special drugs.
Because of disease complexity and heterogeneity, multiple sclerosis pathogenesis remains unknown, and, despite extensive research efforts, specific and effective treatments have not yet been developed. Efforts for finding suitable effective treatments are being made. We suggest paying attention to VGSCs gating modifiers as a novel and potent strategy for reducing the symptoms of multiple sclerosis disease. Surely, it is necessary to carry out drug design studies in order to find more efficient biocompatible compounds and to do animal studies before using these drugs in humans.
1. : Symptomatic therapy and neurorehabilitation in multiple sclerosis. Lancet Neurol 2005; 4:643–652Crossref, Medline, Google Scholar
2. : The pathophysiology of multiple sclerosis: the mechanisms underlying the production of symptoms and the natural history of the disease. Philos Trans R Soc Lond B Biol Sci 1999; 354:1649–1673Crossref, Medline, Google Scholar
3. : Voltage-gated sodium channel toxins: poisons, probes, and future promise. Cell Biochem Biophys 2003; 38:215–238Crossref, Medline, Google Scholar
4. : Molecular mechanisms of neurotoxin action on voltage-gated sodium channels. Biochimie 2000; 82(9–10):883–892Crossref, Medline, Google Scholar