U of A study sheds light on multiple sclerosis

Key protein may offer insight into how MS develops

Researchers at the University of Alberta have dug down to the cellular level to discover an unusual mechanism in the brain that may offer new insight into how multiple sclerosis develops.

Using tissue samples from the brains of deceased MS patients, the researchers identified a key protein that seems to set in motion a damaging interaction that ultimately leads to “cellular suicide.”

“The finding, and this is a very novel finding, of our study is that this protein is highly unregulated in MS brains,” said Thomas Simmen, a cell biology professor who served as co-author of the research.

“Two aspects of the MS phenotype get boosted by having too much of this protein. One is that you have … brain cells undergoing unwanted cell death. And secondly, it will also boost inflammation.”

Multiple sclerosis is a type of autoimmune disease, a disorder in which the body’s own immune system turns against healthy cells.

In the case of MS, it is nerve cells that get damaged, causing patients to experience increased disability over time. Treatments are available but there is no cure, and the exact cause of the disease remains a mystery.

Many scientists looking into MS have focused on a component within cells known as the mitochondria, which serves two purposes. The mitochondria is firstly a cell’s power plant — making energy to keep the cell alive — but it also acts a as a kind of “sentinel” that can trigger the cell to die if it becomes stressed by inflammation

The calcium gets transferred over massively, the sentinel sounds the alarm and the cell commits suicide.

or some other factor.

In an effort to better understand how this happens, previous research by the U of A team and others has explored how the mitochondria interacts with another cell component called the endoplasmic reticulum — the part of the cell that stores calcium.

Simmen said some communication between the two components is required because this is how the mitochondria is told to make energy.

“But if the cell gets inflamed, then you get too much interaction, and all of a sudden the endoplasmic reticulum gets glued to the mitochondria and you get kind of a short circuit,” he said. “The calcium gets transferred over massively, the sentinel sounds the alarm and the cell commits suicide.”

Based on this finding, the U of A team decided to begin looking for molecules that might be kickstarting this harmful miscommunication. That led them to identify the protein Rab32, which is found in the brain samples of MS patients but is virtually absent in samples from healthy brains.

The study suggests this deluge of Rab32 is at least one of the culprits involved in sparking the destructive defect.

Co-author Fabrizio Giuliani, the medical director of the northern Alberta MS clinic, said he hopes the research will lead to new drugs down the road that target Rab32 and other proteins that may be at play. “Right now, we don’t have a treatment that is protective of the nerve cells in the brain,” he said.

The team’s research, conducted jointly with scholars at the University of Exeter, is published in the Journal of Neuroinflammation.