Blocking Programmed Cell Death

Cells communicate through chemical signals received by specific receptors on the surface of the cell. Cells have thousands of different “mailboxes” called receptors to receive messages; each receptor responds to one, or possibly a few, specific signals. 

Philippe Monnier studies one particular combination of signal and receptor. The signal is known as repulsive guidance molecule a (RGMa); the receptor is called Neogenin. This signal and receptor combination plays two important roles in the health of nerve cells:

  • It prompts or prevents the process of programmed cell death
  • It stimulates the growth of nerve cells to make connections with other nerves

Chemical signals between retinal cells trigger cell deathProgrammed cell death, or apoptosis, is important to the health of the body. It provides a tool to eliminate damaged or cancerous cells, and it helps shape the body during development (for example, separating the fingers in the developing embryo).  However, in some diseases, particularly neurological diseases, it can also destroy cells that can not be replaced. In the case of glaucoma, optic nerve injuries, and slow progressive retinal diseases like retinitis pigmentosa, slowing or stopping programmed cell death can help preserve vision.
Courtesy of Wei Li, National Eye Institute, NIH, Bethesda, MD

Dr. Monnier has shown that blocking the interactions between RGMa and the neogenin receptor can help prevent cell death in retinal eye diseases, and in other neurological conditions such as multiple sclerosis and stroke, when studied n the laboratory. It can also be used to promote the growth and connection of new cells. Dr. Monnier continues to work to understand how best to develop this potential therapy, either by modifying the receptor or by targeting the signal.

Dr. Monnier’s research in this area is support by grants from the Canadian Institutes of Health Research, the Foundation Fighting Blindness, Brain Canada and the Heart and Stroke Foundation.