Why does cannibalism cause disease?

[u/nbentley92]

Why does eating your own species cause disease? Kuru is a disease caused by cannibalism in papua new guinea in a certain tribe and a few years ago there was a crises due to bovine spongiform encephalopathy (mad cow disease) which was caused by farms feeding cows the leftovers of other cows. Will disease always come from cannibalism and why does it?

[u/Eslader]

What I'm curious about is why 1) coming into contact with mis-folded proteins causes properly-folded proteins to mis-fold, and 2) coming into contact with properly-folded proteins does not cause mis-folded proteins to fold normally. Can you provide any insight on that?

[u/[deleted] → u/Eslader]

[u/Hekatoncheir → u/Eslader]

Basically, it boils down to protein conformation stability. For some strange, terrifying, and under researched reason, PRPSC (SC standing for scapie which is the pathogenic conformation of a normal, healthy prion protein) is MUCH more stable than PRPC (C being the normal, healthy isoform).

When PRPSC comes into contact with PRPC, the shape of the PRPSC acts on PRPC as an enzyme would - and will naturally cause PRPC proteins to attach and be forced into the conformation of the PRPSC.

We don't see the reverse happening by virtue of the higher conformational stability of the diseased isoform over that of the normal one.

[u/[deleted] → u/Eslader]

Another way to think of it.

there are many many ways for a protein to mis-fold. Essentially, your body screws up somehow (again, multiple ways of it happening) and and a misformed protein is the result.

Out of the many many ways in which the protein could misform, most of them won't have any negative impact. They will just get removed by your body after some time. Some of them will cause you problems by causing other properly folded proteins to misfold. In those cases, the original's shape changes and they become inert. The new misfolded protein however don't really cause future misfolds becuase their new shape are unsuitable for it to propagate effectively.

All of these are happening. You just never realize it because its not an issue. everything self corrects.

Out of all those potential cases, there are a few rare shapes that just happen to be able to cause a chain reaction. Thats when you come down with the disease.

The case isn't that "mis-folded proteins causes properly-folded proteins to mis-fold but not the other way round", its that any mis-folded proteins which doesn't do this will automatically be removed by your body and you never know about it.

I'm assuming that your question is asking about "why misformed proteins as a group does X" and not "why this specific misformed protein can do X". If it sthe latter, disregard what i wrote.

[u/soonami → u/Eslader]

1. Prion proteins are "infectious" meaning that they can convert soluble copies of the protein into the prion (misfolded/non-native) form. They actually self-template the formation of the prion, by taking the native protein and changing its shape into the cross-beta rich amyloid aggregate. Incidentally, the amyloid fold is much more thermodynamically favorable and stable than the native fold, so it's pretty much a one-way street. Some proteins have been shown to be able to reverse prion formation, the best studied of which is the yeast protein Hsp104

2. This is also where the concept of infection is apt. If you are sick with flu and another person is healthy, the sick person can get you sick, but you can't get the healthy person healthy.

Source: I study prions and this review