Genetic mutations that help animals such as yaks and Tibetan antelopes survive at high altitudes may hold the key to repairing neurological damage in conditions such as cerebral palsy and multiple sclerosis (MS). The findings were published March 13 in the journal Cell Press neuronreveals a naturally occurring pathway that promotes regeneration after nerve injury, potentially opening new doors for treating diseases like MS by harnessing molecules already present in the human body.
“Evolution is a great gift from nature, providing a variety of genes that help organisms adapt to different environments,” says corresponding author Liang Zhang of Songjiang Hospital, School of Medicine, Shanghai Jiao Tong University. “There is still much to learn from naturally occurring genetic adaptations.”
The myelin sheath is a protective layer that surrounds nerve fibers in the brain and spinal cord, allowing efficient transmission of nerve signals. Lack of oxygen during brain development can damage this layer and cause conditions such as cerebral palsy in newborns.
In adults, myelin sheath damage is associated with MS, an autoimmune disease in which the immune system mistakenly attacks and destroys the myelin sheath. Reduced blood flow to the brain, which often accompanies aging, can also damage myelin, leading to conditions such as cerebral small vessel disease and vascular dementia.
In a previous study, researchers discovered that animals living on the Tibetan Plateau, which averages 14,700 feet above sea level, carry a mutation in a gene called Resat. Scientists suspected that this mutation might help animals such as yaks and Tibetan antelopes maintain healthy brain function despite chronically low oxygen levels.
Chan and his team set out to investigate whether this mutation could prevent damage to the myelin sheath. The researchers exposed newborn mice to hypoxic conditions equivalent to altitudes of more than 13,000 feet for about a week. Mice with the Retsat mutation performed significantly better on tests of learning, memory, and social behavior than mice with the standard version of the gene. Brain analysis also revealed that the high-altitude mice had higher levels of myelin around nerve fibers.
The researchers then investigated whether the Retsat mutation could repair myelin sheath damage similar to that seen in MS. They found that in mice with this mutation, myelin sheaths regenerated much faster and more completely after injury. More mature oligodendrocytes, a type of cell responsible for producing myelin, were also present at the injury site.
Further research revealed that mice with this mutation produced higher levels of ATDR, a vitamin A-derived metabolite, in their brains. The Retsat mutation appears to increase the activity of the enzyme that converts vitamin A to its metabolites, thereby promoting the generation and maturation of myelin-producing oligodendrocytes. When the research team administered ATDR to mice with MS-like disease, the mice showed reduced disease severity and improved motor function.
Current treatments for MS primarily focus on suppressing immune activity, Zhang noted. “ATDR is something we all already have in our bodies. Our findings suggest that there may be alternative approaches to using naturally occurring molecules to treat diseases associated with myelin damage,” he says.
This research was supported by the National Science and Technology Major Project, the National Natural Science Foundation of China, the China Postdoctoral Science Foundation, the Shanghai Postdoctoral Excellence Program, the Shanghai Natural Science Foundation, the 2024 Tibet Autonomous Region Science and Technology Plan Key Research, Development and Transformation Project, the Naval Medical College Basic Medical College Open Research Fund, the Yunnan Provincial Revitalization Talent Support Program Science and Technology Champion Project, and the Yunnan Provincial Revitalization Talent Support Program.
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Reference magazines:
Lee, D. others. (2026). Gain-of-function Retsat mutants due to high-altitude adaptation promote myelination through the dihydroretinoic acid-RXR-γ pathway in neurons. neuron. DOI: 10.1016/j.neuron.2026.01.013. https://www.cell.com/neuron/fulltext/S0896-6273(26)00013-9
