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

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

From First Principles vor 2 Monaten

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1:35:38

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. Summary What myelin actually does
and why losing it disrupts neural communication How multiple
sclerosis damages myelin and why the brain’s natural repair process
eventually fails Why oligodendrocyte precursor cells can remain
present in damaged tissue without successfully rebuilding myelin
Why current therapies are better at slowing further damage than
restoring what has already been lost The challenge of getting drugs
across the blood-brain barrier while maintaining target specificity
How evolutionary pharmacology has previously produced medicines
from adaptations found in snakes and Gila monsters The RETSAT Q247R
variant identified in animals adapted to the hypoxic environment of
the Tibetan Plateau How researchers engineered the high-altitude
variant into mice and tested its effect on myelin The surprising
discovery that neurons — rather than the myelin-producing cells
themselves — generate the key repair signal How RETSAT increases
ATDR, which neurons convert into ATDRA How ATDRA activates RXR-γ in
oligodendrocyte precursor cells and promotes their differentiation
How administration of ATDR promoted remyelination across multiple
preclinical models Why the result is scientifically promising but
still far from a proven human treatment Featured Paper A
gain-of-function Retsat variant from high-altitude adaptation
promotes myelination via a neuronal dihydroretinoic acid-RXR-γ
pathway Neuron, 2026 DOI: 10.1016/j.neuron.2026.01.013 Explore
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