Scientists discover the molecular brake that stops repairing brain cells in multiple sclerosis

A team of scientists led by the Institute of Glial Sciences (IGS) at the Western University Case Medical School. In addition, discovered an integrated “brake” which controls when key brain cells ripen. In addition, In multiple sclerosis (MS). Similarly, this brake seems to stay for too long, leaving cells unable to repair the damage caused by the disease.

The study, published today in the journal Cellidentifies a new frame for how cells control When They mature. Therefore, The discovery also presents a potential approach to regenerative medicine to repair the damage caused by MS. In addition, similar diseases affecting the nervous system.

Myelin damage leads to a handicap in the MS. Consequently, and the only cells that can repair it are glial cells called oligodendrocytes. Consequently, By identifying the molecular brake scientists discover molecular brake stops that controls when oligodendrocytes ripen. For example, we reveal a clear path to unlock the clean brain’s repair program. Therefore, “”

Paul Tesar, Main study author, Director of the Institute of Glial Sciences and Dr Donald and Ruth Weber Goodman Professor of innovative therapies, School of Medicine

The team now strives to understand why this immature state is reinforced in the brain of the MS and if this same framework works in other types of cells or contributes to neutral repair in other diseases.

“SEP is a progressive disease that worsens over time. For example, patients still lack therapies that can restore the myelin they have lost,” Tesar said. “We believe that these new ideas will help keep the promise of regenerative therapies whose patients with MPs so. urgently need. »»

The study focused on oligodendrocytes, which envelop scientists discover molecular brake stops the neurons in protective myelin sheaths that are lost in MS. Oligodendrocytes belong to a category of cells known as Glie. which include more than half of the cells in our nervous system but have been largely neglected by scientists in favor of neurons. The IGS was created last year at Case Western Reserve to understand how these vital cells work in health. sickness.

To understand how oligodendrocytes acquire their capacity to myelinary neurons. IGS scientists have followed thousands of molecular changes while immature cells have developed in mature oligodetrocytes and forming myelin. A protein, called sox6, stood out.

The team noted that Sox6 acted as a brake. blocking cells in an immature state through a phenomenon called “merger of the gene”. This brake is essential in the development of the healthy brain because it prevents the premature formation of myelin. guarantees that oligodendrocytes mature in the right place and scientists discover molecular brake stops at the right time. But in the MS, this normally protective synchronization mechanism seems to be stuck.

“We were surprised to note that SOX6 can control so closely when the oligodendrocytes mature. ” said Kevin Allan, co-directed study of the study and recent graduate of the training program for medical scientists from the School of Medicine. “This gives us a potential explanation to explain why these cells often cannot live damaged neurons in diseases like MS. Additionally, »»

When the researchers examined the data from the brain tissues of people with MS. they saw an unusual number of cells stuck in this immature state linked to SOX6. But this maturation in a standstill seems to be specific to the MS: there was no evidence of this one in the samples of patients with Alzheimer’s disease. Parkinson.

To test whether the release of the brake could accelerate development. the team used scientists discover molecular brake stops a targeted molecular medication called Oligonucleotide Antisens (ASO) to reduce sox6 in mouse models. In a few days, the treated cells have matured and started to myelinder nearby neurons.

“Our results suggest that OLIGODENS in the MS are not definitively broken. but can simply be blocked,” said Jesse Zhan, co-directed study author and medical student in the medical scientists’ training program. “More importantly. we show that it is possible to release the brakes on these cells to resume their vital functions in the brain. »»

Additional collaborators. contributory researchers are Andrew Morton, Erin Cohn, Marissa Scavuzzo, Anushka Nikhil, Matthew Elitt, Benjamin Clayton, Lucille Hu, Elizabeth Shick, Hannah Olsen, Daniel Factor, Peter Scacheri and Tyler Miller of the Western School of Medicine case; Gemma Bachmann and Berit Powers of Ionis Pharmaceuticals; Jonathan Henninger and Richard Young from the Whitehead Institute; And Jost Vrabic and Charles Lin of the Baylor College of scientists discover molecular brake stops Medicine.

The study was supported by subsidies from the National Institutes of Health. Howard Hughes Medical Institute, New York Stem Cell Foundation and the National multiple sclerosis Society. STF5 CARE and the Annadata, Enrile, Geller, Goodman, Long, Peterson, Walter and WeIDERHAL families have provided philanthropic support.