: Why do prion diseases have 100% fatality rate ?

Question

I recently found out about the so-called prion diseases, which are incurable and fatal diseases that affect (a euphemism, the real word is destroy) the CNS and cause a rapid deterioration of mental and physical abilities.

There are many prion diseases, the two most famous are probably the mad cow disease (non-human mammals), and the Creutzfeldt–Jakob disease (CJD) (for human mammals). Both are 100% fatal, and *no one* is known to have survived longer than 2.5 years after a CJD diagnosis. That’s the kind of stuff you wouldn’t wish on your worst enemy.

Why are these diseases so deadly? I read that it has to do with abnormal proteins but that was way over my head.

EDIT : I have another question, can prion diseases be rightly called the most dangerous diseases known to man ?

Thanks;

In: Biology

Answer 1

I think the best way to understand the ‘misfolded proteins’ is it comes down to entropy. It’s not that they’re just ‘misfolded’ and can be ‘unfolded’, because that misfolded state is the most ‘ordered’ state (at least in the biochemical sense, even if not at the ‘physics’ or ‘chemical’ level).

Proteins have multiple ‘levels’ of organisation, at the first level, it’s the string/chain of amino acids, at the next level we make basic protein structures/shapes (based on that string of amino acids), at the level after that those proteins come together and make bigger complex structures (normally due to interactions between amino acids in those simple shapes), and at the fourth level multiple complex structures come together and make bigger structures. Those final levels of shape and the amino acids that present to the outside or inside of the protein is what allows for specific interactions with other cells/molecules.

Normally, we can denature proteins with heat, enzymes, etc. but with prions their structure is dysfunctionally strong. It’s like a black hole for proteins in a sense, and other proteins that come in contact with it can become amalgamated as well as they ‘pass the event horizon’ and can’t escape.

I’m not sure if black holes are understandable by a 5yo but that’s my best attempt. XD