Comment by subroutine | Hacker News Reader

Comment by subroutine | Hacker News Reader

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Proteins have a half life of ~24 hours. CJD has an incubation period of roughly 10 years. If de novo PrP synthesis was somehow halted, the likelihood of developing CJD would drop to zero.

On the other hand whatever job PrP was doing will also cease getting done, and its downstream pathways will be disrupted. So there are likely consequences.

Now if you could totally shut down PrP synthesis for like a week, then turn it back on, that might work. In theory this is possible using a tet-expression system [1], but I've never worked with a tet system that wasn't leaky. The only sure way would be to KO PrP genes from all cells, then CRISPR it back in a week later. Oh, and I'm talking about cells in a culture dish; this strategy would never work in an adult human.

[1] https://www.jax.org/news-and-insights/2015/april/introductio...

> Proteins have a half life of ~24 hours.

All of them? I admit that I'm not a biologist, so that's new to me, but this would seem to put our bodies under immense stress if we had to replace half of all our proteins every day. If the average human body has 10 kg of proteins, this would mean the necessity of synthesizing 5 kg per day to prevent your death. Or is this specifically about PrP? If it's true that it doesn't last long, then perhaps stopping its synthesis would be a viable option.

Does the misfolded PrP have a different half-life?

There is certainly a large standard deviation on that 24 hour average. Some proteins might last a few days. But we are talking on the order of days vs. the disease which takes on the order of years to manifest. Anyway I assume that the disease manifests as a result of bad PrP accumulation (much like how tau and Abeta protein accumulation eventually results in Alzheimer's disease; in fact Abeta has been described as having "prion like" properties regarding how Abeta clusters beget more clusters). So as soon as you shut down PrP synthesis, I doubt CJD could manifest, even if the current PrP in your body was immortal.

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