I remember hearing that prions like mad cow disease are misfolded proteins that manipulate other proteins they come into contact with. If that’s the case why can’t you use another prion to unfold it and restore it to normal?
In: Biology
Imagine you made a paper plane, and someone came over and crumpled it into a ball. Can you un-crumple it? Yes. Can you make it a plane again? Well…maybe, with a lot of time and effort.
Proteins may need chaperones, which are other proteins, to fold properly. These chaperones make sure that the protein is the shape it is supposed to be – a bit like you making that paper plane. Each protein has a different function, and therefore needs to be folded a different way. To re-fold it, you might need to identify, recreate, and reintroduce chaperones – and if important molecules like sulfur, nitrogen, etc. are lost in the protein, you’d need to find a nontoxic way to add them back on. You would also have to undo the incorrect folding without messing up the other proteins around it. In labs, we use things that break down bonds between proteins so that they lose their shape (denaturing), and when we do this, all of the proteins denature. You would have to make something that can target just that one specific misfolded protein and not denature other proteins, and I have no idea if that’s possible with the technology we have right now.
this isn’t exactly ELI5, but basically when the prion causes a misfold, it makes the protein go into a low energy confirmation. Thnk about spilling a glass of milk: before the milk is spilled, it’s organized in the glass. When it’s spilled, it’s chaotic and all over. It would take a lot of energy to get it all back into the glass just the way it was. It’s more stable out of the glass than when glass was there. It’s the same with the protein, since it’s more stable misfolded it would take a pretty powerful enzyme to correct it, and how do we even know what’s ‘correct’?
If my answer is weird or wrong someone please let me know, that’s how I understood it from biochem but it’s been a hot minute.
We know of many protein folding chaperones that can do this intracellularly. Another hurtle to overcome is early diagnosis. vCJD “human mad cow” may have these misfolded, contagious proteins build up over months, years, or even decades. By the time signs and symptoms are diagnosed (through brain biopsy), brain tissue death is usually high and prognosis is poor. There is a genetic disorder Creutzfeldt Jacobs Disease that this disorder is inherited through a mutation in the neural protein. Further research here could give us some additional answers.
A paperclip is a wire that has been bent in a particular way. Unbend one, and then try to bend it back into its original shape. You might get close, but without special machines, you’ll never get it exactly right.
Proteins are millions of times more complicated than paperclips, and we really don’t even really know how they’re folded to begin with, so right now it would be impossible to unfold one and put it back to where it was before. It’s possible that sometime in the future we might figure it out, but there are a lot of things we need to learn first.
Its theoretically possible. We just discovered how prion’s work, chemically designing a protein that fixes it is a long way in the future.
As other posters have stated there are more likely easier ways to cure the disease.
We do have proteins that do this, there’s a class of proteins called Heat Shock Proteins that are expressed in response to cell stress (they were discovered by heat shock, but there are actually up regulated by all types of stress!)
You should read the [Wikipedia article](https://en.m.wikipedia.org/wiki/Heat_shock_protein) for a quick intro. That article doesn’t have anything about neural tissues though I think.
The brain is a very special place, it’s possible that heat shock proteins are not expressed in Neurons, so any peptides or proteins which can cross the blood brain barrier (I.e. prions) can go unchecked, but I actually don’t know much about it.
If you’re interested, you can install Folding@home, and contribute your computer’s idle time where the CPU isn’t doing any other work to help compute protein foldings. This project constitutes the single largest focused computing effort on the planet, surpassing all the worlds top super computers in computing power, at least individually.
We have really no idea what shapes proteins are. Folding@home is all about simulating the atoms to try to find structures that are the most stable and have the lowest ground state. These are LIKELY the shapes of our proteins. And bear in mind there can be multiple stable states, not just the lowest ground state, and once you figure out what all they can be, you then need to figure out which shapes are actually used in our bodies, and which are the prions.
So yeah, we’re just not far along enough in this effort.
ELI5: What’s a Prion?
In chemistry, there are some changes that are for all intents and purposes, one way tickets. As a classic example, think about cooking an egg. You didnt add anything to the egg except heat. All the original parts of egg are still there, but they’re arranged in such a way now that you cant “uncook” it in any practical sense. When you cook an egg you’re actually doing something sort of similar to what prions do to proteins. So while cooking an egg is as simple as “apply heat”, and folding a protein the wrong way is as simple as “apply prion”, reversing those changes requires much more effort to the point if being practically impossible.
Think of a pipe cleaner that is twisted and folded. It’s trivial to go and pull it straight, but try and recreate EXACTLY how it was twisted and folded before, and you’re going to have some difficulties. Proteins have thousands of types of folds, so building all the folds in a protein from scratch would require more than a simple enzyme.
Latest Answers