Multiple sclerosis is a serious neurological condition for which there is no known cure. While the causes of the disease remain relatively unknown, we do know that, in individuals with MS, the immune system attacks the protective sheaths around nerve fibers. New research has uncovered how the formation of these myelin sheaths is regulated by protein molecules.
Think of the human brain as a computer in which the individual processors are efficiently connected using high speed cables. The approximately 100 billion nerve cells are the processors, and the nerve fibers (axons covered by myelin sheaths) are the fiber-optic cables. How quickly data can be passed is very dependent on the quality of the myelin sheaths. Damage to these – or to the cells that produce them – leads to serious disorders like MS that, eventually, destroy the nerve cells entirely.
Oligodendrocytes and Nfat Proteins
A team of researchers is looking at how oligodendrocytes regulate the formation of these myelin sheaths, with hope that this understanding will further develop knowledge of neurological disorders like MS. They have successfully identified protein molecules (like Sox10) that regulate the creation and preservation of myelin sheaths, but they wanted to go a step further and try to understand how the proteins interact when myelin is formed.
In the course of their research, they found that other molecules, called Nfat proteins, are necessary for the success of the interaction between the known molecules. The existence of Nfat proteins in oligodendrocytes allows the other required protein molecules to coexist without displacing one another.
Targeting Nfat Proteins
This research is closely linked with other research that aims to target stimulation of Nfat proteins in the hopes of promoting the formation of new myelin sheaths in MS patients. This type of stimulating substance is not yet available, however.
So far, only substances that inhibit the activity of these Nfat proteins have been developed, and are used in medicines like Cyclosporin A and Tacrolimus to keep the immune system in line to prevent organ rejection in transplant patients, for example. It is interesting to note that these patients often suffer from neurological disorders resulting from myelin sheath loss.
The new research suggests that serious side effects of current medications aimed at inhibiting Nfat proteins include myelin sheath loss, resulting in serious neurological conditions, making it absolutely critical that further research is performed as quickly as possible to improve existing medications.
These findings also show just how important Nfat proteins are for myelin formation, which opens up an entirely new approach to finding treatments to neurological disorders like MS that currently have no cure.
Further Reading & References:
Matthias Weider, Laura Julia Starost, Katharina Groll, Melanie Kspert, Elisabeth Sock, Miriam Wedel, Franziska Frb, Christian Schmitt, Tina Baroti, Anna C. Hartwig, Simone Hillgrtner, Sandra Piefke, Tanja Fadler, Marc Ehrlich, Corinna Ehlert, Martin Stehling, Stefanie Albrecht, Ammar Jabali, Hans R. Schler, Jrgen Winkler, Tanja Kuhlmann, Michael Wegner. Nfat/calcineurin signaling promotes oligodendrocyte differentiation and myelination by transcription factor network tuning. Nature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-03336-3
University of Erlangen-Nuremberg. ”Our vulnerable nervous system: What affects its protective sheaths? Researchers shed light on a complex biochemical mechanism.” ScienceDaily. ScienceDaily, 8 May 2018. www.sciencedaily.com/releases/2018/05/180508081453.htm.
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