Identifying New Molecular Mechanisms that Promote Myelin Maintenance and Remyelination
Principal Investigator: Dr. Timothy Kennedy
Affiliation: Montreal Neurological Institute, McGill University
Term: April 1, 2017 – March 31, 2020
Keywords: Remyelination, repair, netrin-1
- Myelin is the protective covering around nerve fibers that is damaged in multiple sclerosis (MS). Researchers are actively looking for cellular molecules that regulate the production and repair of myelin in conditions such as MS.
- Netrin-1 is a molecule that has been identified to maintain healthy myelin. However, how it regulates myelin or influences remyelination is unknown.
- The research team will:
- Determine the molecular mechanisms underlying netrin-1 and the molecules it interacts with in promoting myelin maintenance and stability in animal models of MS.
Myelin is the protective covering that surrounds nerve fibers and is produced by cells called oligodendrocytes. Dr. Timothy Kennedy studies the pathways of repair in the brain, in particular the connections between oligodendrocytes and nerve fibers. His central theory is that a protein named netrin-1 and its interacting molecules (called DCC and UNC5B) expressed by oligodendrocytes are critical for myelin maintenance in the central nervous system, and that these proteins also regulate remyelination. He has previously found netrin-1 plays an important role in myelin production and repair processes. His group is working to understand how netrin-1 contributes to the initial formation and maintenance of myelin during development, and in the adult brain, and how targeting the function of these proteins may promote remyelination. In the past year, the research team has discovered that an interacting protein of netrin-1 is required to maintain normal myelin and functions through mitochondria, the critical energy powerhouse of the cell. Ongoing research will examine how specific energy demands influence myelin maintenance and how this process can be manipulated to promote remyelination. By figuring out these repair mechanisms, in particular the role that netrin-1 and its interacting molecules plays, Dr. Kennedy and his team may enable the development of treatments that can enhance myelin repair, which is a vital step in preventing further damage, slowing disease progression and allowing people with MS to regain function.
Potential Impact: Identify new therapeutic targets that could be manipulated to prevent demyelination and promote remyelination as a treatment for MS.
Project Status: In Progress