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2026

Nat Commun 2026 May 25. doi: 10.1038/s41467-026-73381-w. Online ahead of print.

SNAP-23 mediated vesicular trafficking in oligodendrocytes is necessary to maintain adult myelin integrity in mice

Chun Hin Chow, Mengjia Huang, Aryan Regmi, Jayant Rai, Hidekiyo Harada, Sarah Eide, Hong-Shuo Sun, Zhong-Ping Feng, Philippe P Monnier, Kenichi Okamoto, Liang Zhang, Olga L Rojas, Shuzo Sugita

Division of Experimental & Translational Neuroscience, Krembil Brain Institute, University Health Network, Toronto, ON, Canada. Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada. Krembil Research Institute, University Health Network, Toronto, ON, Canada. Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada. Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada. Department of Molecular Genetics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada. Donald K. Johnson Eye Institute, University Health Network, Toronto, ON, Canada. Department of Anatomy, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada. Department of Ophthalmology & Vision Sciences, University of Toronto, Toronto, ON, Canada. Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada. Division of Experimental & Translational Neuroscience, Krembil Brain Institute, University Health Network, Toronto, ON, Canada. Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada. Division of Experimental & Translational Neuroscience, Krembil Brain Institute, University Health Network, Toronto, ON, Canada. Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

Service type: Knockout mice

Abstract

Adult myelin is dynamic and requires continuous support from oligodendrocytes. Inability to sustain myelin health results in demyelination, evident in multiple sclerosis and neurodegenerative diseases. However, the molecular mechanism by which oligodendrocytes recycle and replenish materials to the myelin sheath remains unclear. Here, we investigate whether the SNARE-dependent vesicular trafficking is important for myelin turnover. We conditionally remove SNAP-23, one of the target SNARE proteins, in mature oligodendrocytes of adult mice. Induction of SNAP-23 deletion causes demyelination within 5-10 weeks. Demyelination is associated with an increase in immune cells, including infiltrated T cells, in the brain. Mechanistically, the removal of SNAP-23 in oligodendrocytes impairs vesicle fusion to the myelin and causes the accumulation of myelin proteins within the cells. Taken together, we show that SNAP-23-dependent transport in oligodendrocytes is necessary for adult myelin maintenance, with failure in vesicular transport leading to demyelination and subsequent neuroinflammation.