Unravelling Myelin Stability
New lab model identifies how brain cells maintain myelin, and how breakdown may lead to MS.
Myelin is critical for efficient electrical signalling in the nervous system. When myelin is lost, like in multiple sclerosis (MS), neuron-to-neuron communication is disrupted, leading to symptoms such as muscle weakness, pain, and mood changes.
Oligodendrocytes—supportive cells in the brain and spinal cord (the central nervous system, or CNS)—play a critical role in maintaining myelin, the protective layer that surrounds nerve fibres. Loss or damage to myelin is a hallmark of neurodegenerative diseases such as multiple sclerosis (MS).
“During myelin formation, oligodendrocytes use a process called vesicle trafficking to deliver materials needed to build the myelin layer in cellular packages,” said first author Chun Hin Chow. “It was not clear whether this same process continues to maintain myelin once formed.”
To address this gap, Dr. Shuzo Sugita and colleagues at UHN’s Krembil Brain Institute (KBI) identified a mechanism by which oligodendrocytes maintain myelin in the adult brain—and how disruption of this process may contribute to disease.
In a new study published in Nature Communications, the team developed an experimental model that enabled them to switch off a protein called SNAP-23 after myelin formation was complete. SNAP-23 is part of a group of proteins called SNAREs. These proteins allow vesicles—small membrane-bound packages that carry materials inside cells—to fuse with their target and release their contents.
When SNAP-23 was turned off, myelin broke down within a few weeks. The loss of myelin was accompanied by structural and functional changes in the CNS similar to those seen in diseases such as MS and Alzheimer disease. The researchers also observed a buildup of myelin-related proteins within oligodendrocytes, suggesting that other SNARE proteins may not compensate for the loss of SNAP-23.
Together, these findings suggest that vesicle trafficking is essential for maintaining myelin in adulthood, and that this process is SNAP-23 dependent.
The team also observed increased inflammation and immune cell activity in the CNS after SNAP-23 was disabled—another hallmark of demyelinating neurodegenerative diseases like MS. Compared with other models, the KBI team’s SNAP-23 model did not require external immune modification and produced an immune response soon after myelin loss, making it more representative of what happens in human neurodegenerative processes.
By uncovering how myelin maintenance breaks down, the study provides new insight into the early stages of diseases like MS. The results also highlight SNAP-23–dependent trafficking as a potential therapeutic target, offering a new strategy that could slow or prevent myelin loss at an early stage of disease.
Chun Hin Chow, Graduate Researcher at UHN’s Krembil Brain Institute and PhD candidate at the University of Toronto, is the first author of this study.
Drs. Shuzo Sugita and Olga Rojas, Senior Scientist and Scientist, respectively, at UHN’s Krembil Brain Institute, are the senior and corresponding authors on this study. Drs. Sugita and Rojas are also a Professor of Physiologyu and an Assistant Professor of Immunology, respectively, at the University of Toronto’s Temerty Faculty of Medicine.
This work was supported by the Natural Sciences and Engineering Research Council of Canada, the Canadian Institutes of Health Research, the Krembil Foundation, the University of Toronto, and UHN Foundation.
Chow CH, Huang M, Regmi A, Rai J, Harada H, Eide S, Sun HS, Feng ZP, Monnier PP, Okamoto K, Zhang L, Rojas OL, Sugita S. SNAP-23 mediated vesicular trafficking in oligodendrocytes is necessary to maintain adult myelin integrity in mice. Nat Comms. 25 May 2026. DOI: 10.1038/s41467-026-73381-w.