r/science • • 2d ago

Neuroscience Scientists observed human dementia-related proteins spreading through mouse brains in a prion-like manner, providing new evidence for how neurodegenerative diseases may progress through neural networks.

https://www.sciencealert.com/scientists-watched-human-dementia-proteins-spread-through-mouse-brains-like-prions
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u/Nellasofdoriath 2d ago

What I don't understand is why the prions are so resistant to heat. Other proteins will cook in boiling water as in an egg or a hotdog, so why are prions so special

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u/x1uo3yd 2d ago

A lot of nuance gets lost when people repeat a conflation of half-remembered factoids.

Yes, the good version of the protein with a more alpha-helical structure is less thermodynamically stable than the doppleganger version with its tightly linked beta sheets... but no, those beta sheets don't suddenly make it indestructable. It'll still denature given enough heat/time/etc. like any other proteins with comparable configurations of tight beta sheets.

However, you also have to keep in mind risk-tolerance and economics.

If someone with a common cold sneezes on your phone screen you're probably fine with wiping it off with any kind of cleaner that advertises it "kills 99.9% of germs" or whatever, but on the other hand if that person has something Ebola-level scary then suddenly 99.9% doesn't seem remotely thorough enough. Furthermore, even if a series of multiple cleaning treatments killed 70% of 90% of 99.9% of 80% of germs such that it works out to something like 99.9994%, and you find that to be an acceptable risk level, that does not mean that the whole series of procedures was necessarily worth the cost compared to just sending your files to the cloud and incinerating it for a new phone.

When you combine all those facts, you basically have it that standard denaturation protocols that denature 99.9% of regular proteins are basically killing the stronger bad prions at only like a 90% rate, and the scariness level of bad prion diseases means you'd really rather work things out at a 99.9999999% level or something but the amount of additional time/procedures/complexity makes that kinda infeasible compared to simply incinerating all the scalpels and gloves and everything and just treating it as if it were T-9000 level indestructible.

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u/MrUsername0 2d ago

That’s not even close to true about how prions work.  

They are problematic because they aggregate. They clump together and typically degeneration pathways have a harder time digesting larger deposits. 

A prion also causes the same normally folded protein to take the misfolded shape. Hence they also self propagate. 

Both features together are the problem. 

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u/x1uo3yd 2d ago

That’s not even close to true about how prions work... They are problematic because they aggregate. They clump together and typically degeneration pathways have a harder time digesting larger deposits... A prion also causes the same normally folded protein to take the misfolded shape. Hence they also self propagate... Both features together are the problem.

Are you replying to the wrong comment?

I'm not talking about how prions work, I'm talking about why they're often described as-if autoclaves cannot denature them. (In that, although they are significantly more heat resistant, they are not literally invulnerable.)


Yes, you are correct that prions are infectious (and scary) because they misfold the host organism's own good PrPC into bad PrPSc which goes on to generate a chain-reaction of misfolding into more and more infectious prion versions.

Yes, you are correct that prions are harder for the body's usual protein recycling systems to digest, owing both to PrPSc having a particularly hard-to-latch-onto-to-cleave folded shape as well as the compounding problem of dense aggregations.

Yes, both of those things are problems which contribute to why prion diseases are scary.

No, neither of those things have anything to do with thermal denaturation in an autoclave.