Myelin is a lipid sheath that insulates nerve fibers carrying signals throughout the brain and body. When this sheath becomes damaged, the passage of these crucial signals is disrupted, leading to neurological disorders.
Now, researchers have identified a genetic mutation that helps some animals repair their myelin. The team, reporting in the journal Neuron, hopes their findings could accelerate the regeneration of damaged myelin in humans.1
Myelin Damage in Disease
Damage to myelin underlies several neurological conditions. In multiple sclerosis (MS), autoimmune attacks degrade myelin, causing problems with cognition and movement. In cerebral palsy, myelin is damaged during development, frequently leading to lifelong movement and cognitive disabilities. In old age, impaired blood flow can also wound myelin, adding to the disease burden of conditions like vascular dementia and cerebral small vessel disease.
An environmental factor that can easily damage myelin is hypoxia. Researchers have long wondered how some animals thrive in low-oxygen environments, such as the Tibetan Plateau. Here, the average elevation is a lofty 14,700 feet, but this doesn’t seem to bother beasts like the yak or the Tibetan antelope.
Previous research had identified that these animals have a mutation in a gene called retinol saturase (Retsat).2 This gene encodes a protein linked to lipid metabolism. Researchers suspected this mutation might be key to how high-altitude animals maintain myelinated brain signaling even in hypoxic environments.
A Naturally Occurring Restorative
In the new study, researchers tested the role of the Retsat mutation by exposing newborn mice with and without the mutation to hypoxic conditions that mimicked an elevation of 13,000 feet. After a week of exposure, they tested their mice on learning, social behavior, and memory tasks. Mice that carried a Retsat mutation performed better in all of these tests. Subsequent analysis showed that these mice had higher levels of myelin in their brains.
The team also studied how mice with the Retsat mutation responded to myelin damage mimicking that seen in MS. Compared to control mice without the mutation, these mice’s myelin sheaths regenerated faster and more completely after injury. The injury sites also contained a greater number of myelin-producing mature oligodendrocytes.
The team found that mice with the Retsat mutation had higher levels of a brain metabolite called all-trans-13,14-dihydroretinol (ATDR). This chemical, derived from vitamin A, appeared to promote the production and maturation of these oligodendrocytes.
The researchers noted that most current treatments for MS work by suppressing the immune system rather than by exploiting endogenous processes. “ATDR is something everyone already has in their body. Our findings suggest that there may be an alternative approach that uses naturally occurring molecules to treat diseases related to myelin damage,” said Liang Zhang, a study coauthor and neuroscientist at Shanghai Jiao Tong University, in a statement.
When the researchers gave ATDR to mice with a disease that mimics MS, their symptoms decreased and their motor function improved.
The team hopes that future genetic studies could reveal other ways to help the body fight disease. “Evolution is a great gift from nature, providing a rich diversity of genes that help organisms adapt to different environments,” said Zhang. “There is still so much to learn from naturally occurring genetic adaptations.”
- Li D, et al. A gain-of-function Retsat variant from high-altitude adaptation promotes myelination via a neuronal dihydroretinoic acid-RXR-γ pathway. Neuron. 2026.
- Xu D, et al. A single mutation underlying phenotypic convergence for hypoxia adaptation on the Qinghai-Tibetan Plateau. Cell Res. 2021;31:1032-1035.
