Targeting Oligodendrocyte Maturation for the Study of Axonal Survival
Principal Investigator: Dr. Wolfram Tetzlaff
Affiliation: The University of British Columbia
Term: April 1, 2016 – March 31, 2019
Keywords: demyelination, cuprizone, axonal degeneration, oxidative stress
- One hallmark of multiple sclerosis(MS) is that the nerve cell processes lose their surrounding insulation material, called myelin, leading to a greater risk of demyelination and neurodegeneration.
- MYRF is a molecule that is downregulated in MS lesions of humans. It has also been shown to promote repair in mice. A better understanding of the role of MYRF in MS is needed.
- The research team will:
- Remove MYRF in an animal model system to test which drugs will prevent demyelination of neurons.
Myelin loss often leads to damage to nerve fibers, rendering them unable to communicate with one another and causing them to die (neurodegeneration). This loss of nerve fibers is thought to underlie the progressive course of MS. Previous research has identified a key molecule involved in the repair processes called MYRF. In the previous two years, Dr. Wolfran Tetzlaff and his research team used genetically engineered mice lacking MYRF and discovered that MYRF is required to promote remyelination. Furthermore, the team has removed MYRF from remyelinating cells to show inhibition of the remyelination process. These findings are interesting as there are low levels of MYRF in brain lesions of humans with MS. Therefore, stimulating the expression of MYRF may help to overcome the remyelination failure in humans. The Tetzlaff research team now hopes to use this established model system that prevents remyelination with the removal of MYRF to test which drugs will preserve the demyelination of neurons.
Potential Impact: Insights gained from this project may help with stimulation paradigms for humans with MS to promote remyelination.
Project Status: In Progress