As they find out more about the cell biology of multiple sclerosis, scientists are gradually unraveling the mysteries of the disease, although the exact causes are still unclear. Now, a new study continues this progress with a significant discovery about a new cellular mechanism. It suggests that high levels of the protein Rab32 disrupt key communications involving mitochondria. The disruption causes these “cellular batteries” to misbehave, leading to the toxic effects seen in the brain cells of people with multiple sclerosis.
The new study is the work of researchers from the University of Exeter in the United Kingdom and the University of Alberta in Canada. They report their findings in the Journal of Neuroinflammation.
Co-author Paul Eggleton, an immunologist and professor at the University of Exeter Medical School, says that multiple sclerosis can have a “devastating impact on people’s lives,” and yet, unfortunately, the present situation is that “all medicine can offer is treatment and therapy for the symptoms.”
As the disease progresses, it destroys more and more of the fatty myelin sheath that insulates and protects the nerve fibers that send electrical messages in the central nervous system.
This destruction can lead to brain damage, vision impairment, pain, altered sensation, extreme fatigue, problems with movement, and other symptoms.
As research into the cause of MS progresses, scientists are becoming increasingly interested in the role of mitochondria – the tiny components inside cells that produce units of energy for powering the cell.
- More than 2.3 million people worldwide are living with MS.
- The disease affects two to three times more women than men.
- Although genes are likely to have a role, there is no evidence that MS is inherited.
In earlier work, the team behind the new study was the first to provide an explanation for the role of defective mitochondria in MS through clinical and laboratory experiments.
In their new investigation, the researchers
They found that levels of Rab32 are much higher in the brains of people with MS and hardly detectable in brains of people without the disease.
They also discovered that the presence of Rab32 coincides with disruption to a communication system that causes mitochondria to malfunction, causing toxic effects in the brain cells of people with MS.
The disruption is caused by a cell compartment called the endoplasmic reticulum (ER) being too close to the mitochondria.
The ER produces, processes, and transports many compounds that are used inside and outside the cell.
The researchers note that one of the functions of the ER is to store calcium, and if the distance between the ER and mitochondria is too short, it disrupts the communication between the mitochondria and the calcium supply.
Calcium uptake into mitochondria is already known to be critical to cell functioning.
Although they did not discover what causes Rab32 levels to increase, the team believes that the problem may lie in a defect in the base of the ER.
The study could help scientists to find ways to use Rab32 as a treatment target, as well as look for other proteins that may cause similar disruptions, note the authors.
“Our exciting new findings have uncovered a new avenue for researchers to explore. It is a critical step, and in time, we hope it might lead to effective new treatments for MS.”
Prof. Paul Eggleton