A gain-of-function Retsat variant from high-altitude adaptation promotes myelination via a neuronal dihydroretinoic acid-RXR-γ pathway - PubMed
4 hours ago
- #evolutionary adaptation
- #myelination
- #white matter
- A gain-of-function Retsat variant (Q247R) from high-altitude adaptation promotes CNS myelination and repair.
- Mice with the Retsat variant show reduced neonatal hypoxia-induced hypomyelination and enhanced remyelination in adulthood.
- The variant increases neuronal production of all-trans-13,14-dihydroretinol (ATDR), acting non-cell autonomously.
- ATDR is converted in neurons to all-trans-dihydroretinoic acid, activating the RXR-γ pathway in oligodendrocyte progenitor cells.
- ATDR administration promotes remyelination in multiple myelin injury models.
- Retsat and dihydroretinoids are identified as key regulators of white matter integrity and potential therapeutic targets.