Multiple Sclerosis Society of Canada

Targeting novel functions of cysteine cathepsins to limit neuroinflammation

Principal Investigator: Dr. Robin Yates

Affiliation: University of Calgary

Term: April 1, 2016 – March 31, 2019

Funding: $346,506

Keywords: cathepsin z, dendritic cell, macrophage, inflammasome, demyelination

Summary:

  • During inflammation, molecules called cytokines are released by immune cells and these molecules are used to communicate with other immune cells, guiding them to the damaged brain cells and bringing more immune cells into the brain. One major cytokines that causes inflammation and damage to the brain in multiple sclerosis (MS) is IL-1 and a protein called cathepsin Z stimulates the release of IL-1.
  • How cathepsin Z regulates the function of IL-1 is unknown.
  • The research team will:
    • Investigate how cathepsin Z is involved in the production of IL-1 and the mechanisms regulating this interaction.

Project Description:

Inflammation in MS is caused by cells of the immune system traveling to the brain and releasing molecules called cytokines. These cytokines are used by immune cells as a way to communicate with each other, and in MS they can prompt immune cells towards sensitive brain cells eventually resulting in damage and inflammation to the central nervous system. One important cytokine in MS is IL-1. Dr. Robin Yates’ research group has evidence to suggest that a protein called cathepsin stimulates the release of IL-1 and that mice that don’t have this protein show lower levels of brain inflammation and a milder MS-like disease course. Dr. Yates’ research will break down the role and mechanism of action of cathepsins in MS. In the past year, the research team has identified the involvement of a particular cathepsin in triggering IL-1 activation. This discovery will pave the way for further understanding of the development of MS and will help explain why some courses of MS are different than others.

Potential Impact: This project has the potential to lead to key discoveries that will allow scientists and clinicians to better understand how MS develops and why some people, but not others, develop and progress in this disease.

Project Status: In Progress