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amaurea t1_jduktyh wrote

Are prions completely absent in healthy individuals? If they're present at low levels, then cannibalism would allow bioaccumulation of them.

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PHealthy t1_jdult22 wrote

Cannibalism is just a form of transmission, prions self propagate by causing misfolding of healthy PrPs which accumulate into amyloids and cause disease.

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amaurea t1_jduoxhb wrote

I think we're talking past each other because some basic assumptions are left unstated. I think these are:

  • Healthy individuals have zero prions
  • The body cannot defend against any level of prions. Once they're in, they're bound to replicate until they reach fatal levels.

If those are true, then I agree that transmission is all that matters. If they aren't true, then the prion level would matter, and bioaccumulation (or really biomagnification) could come into the picture. I read something recently about defense mechanisms called "chaperones" that restore prions to the correct shape. It would also be odd for cells to have no defense against a problem that's surely been around for billions of years. So that's the background for my question.

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Chiperoni t1_je515ou wrote

As far as we can tell, you can't fix a misshapen PrP (aka prion). Those "prions" in the paper you are referencing are yeast proteins that have distinct conformations that can propagate like human prions. All humans have tons of PrP but it's rare for one to become a prion. However, once one does it can start a chain reaction.

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amaurea t1_je55u76 wrote

>Those "prions" in the paper you are referencing are yeast proteins that have distinct conformations that can propagate like human prions.

Thanks, I missed that they were only roughly analogous to prions. That's an important distinction.

And to address my other point myself, it looks like only a few groups of mammals are vulnerable to them, so evolution hasn't had billions of years to work on this, more like tens of millions, I think.

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ReturnToCrab t1_jdz3ef4 wrote

> Are prions completely absent in healthy individuals?

Yes, otherwise everyone would die from them pretty fast. Despite similarities, prions aren't viruses or bacteria, they can't lie dormant

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Chiperoni t1_je51ggf wrote

We have tons of PrP^wt of which it is very rare for one to become PrP^sc . If PrP^sc forms it's estimated to take around a decade to kill, at least in humans.

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