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.

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 FFPffppod.comffppod.com/fundingffppod.com/transfersffppod.com/America250

Support the showffppod.com/donate

Follow@FFPPod on X / Instagram / TikTok / Facebook

Tämä jakso on lisätty Podme-palveluun avoimen RSS-syötteen kautta eikä se ole Podmen omaa tuotantoa. Siksi jakso saattaa sisältää mainontaa.

Jaksot(58)

What OpenAI Actually Did to Navier-Stokes (EP 58)

What does it mean to solve an equation that describes almost every fluid around us, from the air over a wing to the water swirling down a drain?In Episode 58 of From First Principles, Lester Nare and ...

24 Syys 4h 9min

What’s Next in Science? Nobel Prizes, Space Missions & More (EP 57)

What science should you be watching this fall? From Nobel Prize season to NASA’s Roman Space Telescope, Mars’ moons and Mercury, Lester Nare and Krishna Choudhary take a relaxed tour of the discoverie...

14 Syys 1h 3min

Why Spin Qubits Will Win the Quantum Race (Part 2) (EP 55)

Which quantum computer will actually scale?In Part 2 of our quantum computing deep dive, Lester Nare and Krishna Choudhary move from theory to hardware—comparing superconducting qubits, trapped ions, ...

31 Elo 3h 46min

How Quantum Computing Actually Works (Part 1) (EP 54)

Quantum computers do not simply “try every answer at once.” So what do they actually do—and why have governments and technology companies spent billions trying to build them?In Part 1 of our two-part ...

20 Elo 2h 11min

What Claude Actually Did to the Riemann Hypothesis (EP 53)

Claude did not solve the Riemann Hypothesis. But what it actually did may be one of the clearest examples yet of how rapidly AI systems are changing the way difficult mathematics can be attacked.In Ep...

14 Elo 1h 47min

The Amazon’s Hidden Civilization (One Year Anniversary) (EP 52)

In this anniversary episode, Lester Nare and Krishna Choudhary look back at how two longtime friends turned their regular conversations about science into a show now shared by millions of people aroun...

6 Elo 1h 47min

The Tech Elon Has Been Waiting For (EP 51)

What happens when electronics can operate at temperatures hot enough to melt aluminum?In this deep-dive episode, Lester Nare and Krishna Choudhary examine a new high-temperature memory device develope...

31 Heinä 1h 44min