Multiple Sclerosis Society of Canada

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Calnexin Deficiency Leads to Dysmyelination

  • MS Society Funded

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Summary
Edmonton – Researchers have identified a gene that leads to a chain of events which impacts the speed at which messages are relayed in the nervous system.
The work involved a team of researchers – throughout Alberta and around the world and was funded in part by the MS Society of Canada. Allison Kraus, Jody Groenendyk, Karen Bedard, Troy A. Baldwin, Karl-Heinz Krause, Michel Dubois-Dauphin, Jason Dyck, Erica E. Rosenbaum, Lawrence Korngut, Nansi J. Colley, Douglas Zochodne, Simon Gosgnach, Kathryn Todd, Luis B. Agellon, Marek Michalak; The J Biol Chem. 2010 Jun 11;285(24):18928-38.

Details
Researchers wanted to specifically study what would happen if they removed a specific chaperone – called calnexin – from non-human test subjects. They had suspected the results would be fatal, but instead the test subjects had numerous mobility issues such as unstable gaits and legs that dragged. The speed of messages being relayed in the nervous system of the test subjects was delayed as well.  The symptoms displayed are very similar to the symptoms seen in patients with diseases such as Multiple Sclerosis and Charcot Marie Tooth, where myelin becomes impaired. Myelin is the protective coating around neurons and is important because it allows messages to quickly travel within the nervous system.

The research clearly showed for the first time that chaperones impact myelin – something that no one had realized until now.

When chaperone was eliminated, the myelin ended up misfolding and had a wavy appearance instead of a concentric circle appearance or pattern. The original, protective sheath became loose and decompacted. This resulted in the signal travelling in the nervous system to be slower. Until now, no one has ever looked at chaperones and their impact on neuropathy.”

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