The Yak Mutation That Could Help Repair the Brain (EP 56)

What can a yak living thousands of meters above sea level teach us about repairing the human brain?In Episode 56 of From First Principles, Lester Nare and Krishna Choudhary break down a new Neuron paper that traces an evolutionary adaptation found in high-altitude animals to a previously hidden pathway involved in building and repairing myelin.SummaryWhat myelin actually does and why losing it disrupts neural communicationHow multiple sclerosis damages myelin and why the brain’s natural repair process eventually failsWhy oligodendrocyte precursor cells can remain present in damaged tissue without successfully rebuilding myelinWhy current therapies are better at slowing further damage than restoring what has already been lostThe challenge of getting drugs across the blood-brain barrier while maintaining target specificityHow evolutionary pharmacology has previously produced medicines from adaptations found in snakes and Gila monstersThe RETSAT Q247R variant identified in animals adapted to the hypoxic environment of the Tibetan PlateauHow researchers engineered the high-altitude variant into mice and tested its effect on myelinThe surprising discovery that neurons — rather than the myelin-producing cells themselves — generate the key repair signalHow RETSAT increases ATDR, which neurons convert into ATDRAHow ATDRA activates RXR-γ in oligodendrocyte precursor cells and promotes their differentiationHow administration of ATDR promoted remyelination across multiple preclinical modelsWhy the result is scientifically promising but still far from a proven human treatmentFeatured PaperA gain-of-function Retsat variant from high-altitude adaptation promotes myelination via a neuronal dihydroretinoic acid-RXR-γ pathwayNeuron, 2026DOI: 10.1016/j.neuron.2026.01.013Explore FFPffppod.comffppod.com/fundingffppod.com/transfersffppod.com/America250Support the showffppod.com/donateFollow@FFPPod on X / Instagram / TikTok / Facebook