Prions: What's up with them?

Being AP Biology enthusiasts, I'm sure at least a few of you have seen the word "prion" tossed around once or twice. Maybe you're aware of some of the ominous-sounding brain diseases that are connected to them, maybe you know they have something to do with proteins, or maybe you only heard it in reference to the seabirds with the same name (which are pretty interesting creatures in their own right). But either way, I'm guessing that none of you know exactly what a prion is. 

Put simply, a prion is a misfolded protein: a protein which failed to form in the correct 3-dimensional shape. Considering the many other ways in which the human body can make mistakes, at face value, a messed-up protein doesn't really seem like it should be anything special. But what makes prions so unique--and so dangerous--is that they can transmit their abnormal shape to certain types of healthy proteins. 

The basic structure and function of a prion protein.

It's worth noting that currently, no one really knows what initially causes prions to form. All that's known is that they essentially serve as an infectious agent once inside a host, collapsing nearby proteins into the same configurations as themselves. The word "prion" originates from this extraordinary property, deriving itself from "protein" and "infection". Prions stand in stark contrast to every other known infectious agent because they don't have any genetic material, nor do they seem to need it; the exact mechanism that allows them to turn normal proteins into more prions is poorly understood. It's possible that it could have something to do with their amino acid sequence, but scientists remain unsure.

The specific type of protein that's susceptible to becoming a prion and being infected by other prions is simply known as a "prion protein", or PrP, because no one is sure what its normal function in the body is supposed to be. As a matter of fact, it's better understood when it's infectious than when it's healthy. However, while it's not clear how prions do what they do, their effect on the body is easier to understand. Prion proteins are mostly located in the nervous system and brain-- and it's their vital placement that makes prion diseases so deadly.

Prion proteins (stained in red) in the neural tissue of a mouse.

What exactly happens during the onset of a prion disease? First, there's an incubation period which can span over a considerable amount of time, from 5 to 20 years. However, once symptoms begin to appear, the disease progresses quickly. The actual cause of said symptoms is pretty simple: as more proteins become prions, they start to aggregate together into structures called amyloids, which disrupt and damage normal brain tissue. Amyloids can be identified by the "spongy" texture of affected tissue, which is shot through with microscopic holes. This feature is responsible for the scientific name used for most prion diseases: "transmissible spongiform encephalopathies", or TSEs for short. 

Amyloid deposits stained in pink.

Obviously, having abnormal structures jabbing through brain tissue is pretty bad for the patient. To make matters worse, because the infectious agent is a protein, people with functional immune systems aren't any less at risk. The end result of prion infection is that amyloids will continue to accumulate in larger quantities, destroying neurons and causing more and more damage to the brain. Symptoms include personality changes, psychological problems such as depression, and issues with movement, coordination and balance (also known as ataxia); all of these worsen chronically over time. Later stages of the disease involve convulsions, severe mental impairment similar to dementia, paralysis, and eventually death.

You might be wondering how these terrifying diseases can be treated, and I have some bad news about that: currently, they kind of can't be. TSEs often go unnoticed in a host for decades thanks to their long incubation period, there's no known way to reverse or even slow their spread, and an immune response isn't any good when it comes to combating the infection. On top of all this, prion proteins' high stability makes it hard to contain and destroy the particles so the disease doesn't spread to more people. 

So why haven't prions killed us all by now? The answer is simple: they're really rare. Most varieties affect animals such as deer, elk and cows rather than humans, and can't be transmitted between species due to differences in the prion proteins of each. The TSEs that do affect humans aren't that common, only cropping up in one in a million people each year. 

Healthy brain on the right, brain of a mad cow on the left.

There have been some outbreaks of prion diseases that reached epidemic proportions. However, these were caused by highly unsanitary practices of cannibalism, which I really doubt any of you are at risk for. In one rather well-known case, bovine spongiform encephalopathy (also known as "mad cow disease") spread through cow populations rapidly because the cattle were fed the remains of other cattle. In another case, a rare TSE variant called kuru was common among the New Guinean Fore people, who practiced ritual cannibalism; the key factor was the prion-infected brains that they were eating. 

The takeaway from all this is that prions generally seem a lot more threatening than they are. It's true that they have terrifying effects on the body, that they're impossible to treat, and that almost nothing is known about them. It's often conjectured that prions could even be responsible for a real-life "zombie apocalypse", which is understandable considering the similarities of some TSEs to the symptoms of the fictional undead. But in spite of their undeniably scary nature, the risk of prion infection is very low and very rare. You'll be fine, as long as you don't eat someone's brain anytime soon.