Today we're going to talk about probably one of the most fascinating and mysterious topics in biomedicine because incredibly little is known about it. We're going to talk about some proteins that are as mind-blowing as they are damning, capable of behaving like infectious beings and causing lethal diseases for those who suffer from them. Today on Hyperactin, we talk about PRIONS. To begin with, a prion is a protein; in fact, prion comes from “protein-like infectious particle .” Specifically, a prion is a misfolded protein that has the ability to transmit that misfolding to other "healthy" proteins, and this ends up generating a variety of FATAL neurodegenerative diseases in both humans and animals. And now maybe you'll tell me OK SANDRA I'M LOST, what exactly does it mean when a protein is misfolded? Well, it was about time we talked about proteins and their folding on this channel. Okay, let's start with the basics: proteins are essential molecules for cells that perform virtually all of their functions: they form their structures, facilitate the chemical reactions necessary for the cell, transport molecules throughout the body, regulate cell division, and help defend us against infections, among many other things. We could say that if the cell were a company, proteins would be its workers. If we analyze what they are made of, proteins are a chain of a set of smaller “pieces” called amino acids. In other words, amino acids are the building blocks of proteins. We have 20 different types, and different combinations will result in different types of proteins. But it goes further, because proteins are much more than a sequence of amino acids: for a protein to be truly functional, it needs to fold upon itself, adopting a three-dimensional structure. Therefore, each protein has a unique three-dimensional structure depending on the amino acid sequence that forms it, which will cause it to fold in one way or another. This folding isn't something that's done because it makes the protein look prettier, but rather it 's something very delicate and very important, because a protein with a defective structure won't be able to perform its function properly, which can have terrible consequences for the cell. Well, "prions" are a type of protein that are not only misfolded, so they don't fulfill the protein's original function, but they are also capable of transmitting this misfolding to other proteins, "infecting" them. It's a bit like zombies, so as prions encounter healthy proteins, they turn them into "defective" and infectious proteins like themselves. And the question to ask is... where does all this mess come from? Where do prions come from ? It is important to understand that prions are abnormal forms of a normal protein. That is, prions come from proteins that are naturally found in our cells, but that have an altered shape or structure. Although there are other proteins that could act as prions, in this video we're going to focus on the one called cellular prion protein or PRPc, by far the most studied and the one that causes the prion diseases we'll see later. Cellular prion protein (or cPRP) is normally found in the membrane of our cells. Although it is found in various types of cells throughout the body, it is predominantly found in the membrane of our neurons, in the nervous system. To this day, its function is still not fully understood , but it is believed that it may have not just one but several, depending on the area of the body in which it is located. For example, at the level of the nervous system, this protein is believed to be related to the transmission of nerve impulses between neurons, and more broadly, to processes such as memory or sleep-wake cycles. And so far so good, right? We have a normal, everyday protein that performs various functions in different areas of the body… until it messes things up . When the PRPc protein misfolds, it results in a pathological and infectious form of the protein known as PRPSc. The change from PRPc to PRPSc is because the C refers to 'cellular', while the Sc comes from 'scrapie', a prion disease that occurs in sheep. One thing that was hard for me to understand is that CELLULAR PRION PROTEIN is a NORMAL PROTEIN in our body, NOT THE PRION ITSELF, so could the name be more confusing? It is PRPSc that is the prion because it is misfolded. This “malignant” version of the protein, this PRION, is capable of transmitting the misfolding to other proteins and giving rise to a whole series of diseases that ultimately destroy the nervous system. How the prion causes the normal protein to change its conformation and turn to the dark side, resulting in the marked neuronal death it produces, is still a mystery. But there is one more problem. Not only does the protein fold incorrectly, and is capable of transmitting this to other proteins, but the new conformation of these proteins causes them to tend to stick together and form aggregates of bad proteins. To give you an idea, there is a very good example which is a folding chair. We could say that the protein with the correct structure (PRPC) would be equivalent to the unfolded chair, but that when its structure changes (when it becomes PRPSC) it adopts the form of a folded chair. With this new shape, it is easier for the protein to form aggregates with the rest of the defective proteins. The problem with these aggregates is that they are so damn stable and resistant, which makes it impossible for our bodies to break them down. Among other things, these aggregates become resistant to our proteases, enzymes responsible for degrading other proteins. The fact that prions can "infect" other proteins, causing them to change their conformation, that these misfolded proteins clump together to form aggregates, and that our bodies are unable to eliminate them, means that over time, prions cause what are known as transmissible spongiform encephalopathies . Prions cause transmissible spongiform encephalopathies , which are a group of diseases that are so named because 1- encephalopathies: they affect nervous tissue; 2-They produce neuronal degeneration that makes the brain take on a spongy appearance, because “vacuoles” are generated in the brain; 3- They are transmissible from one organism to another. These diseases affect both animals and humans. In animals, probably the best known is bovine spongiform encephalopathy (BSE), which affects cattle. and is popularly known as " mad cow disease" due to the strange behavior and motor problems exhibited by infected cows, in addition to other symptoms such as weight loss, blindness, and eventually death. This disease hit the United Kingdom quite hard in 1986 when the first cases of sick cows were discovered. This "new disease" was later declared, which the cows had acquired after being fed a food medley that, among other things, contained remnants of nervous tissue from sheep with prion disease. Mad cow disease was dangerous because consuming its meat could cause humans to become infected with prions and develop Creutzfeldt-Jakob disease (CJD). This prion disease affects humans and produces symptoms such as rapidly progressing dementia, resulting in memory loss, personality changes, and hallucinations. Later, those affected also develop myoclonus, which are rapid, involuntary muscle movements, similar to what happened to mad cow disease. Although we can develop this disease by eating meat from cows infected by prions, this is not the only possible cause, and that is why there are several types of Creutzfeldt-Jakob disease: there is the sporadic form, which is due to the spontaneous misfolding of the prion protein; Familial prion disease, due to a hereditary mutation in the prion protein gene, which causes the protein to form in an already misfolded state; or acquired, which can be caused by the consumption of infected foods or by other causes such as the transfusion of infected blood. However, Creutzfeldt-Jakob disease (CJD) is not the only type of disease caused by prions in humans. There are also others, such as fatal familial insomnia (FFI), in which sufferers begin with progressive insomnia that gets worse, leading to panic attacks, paranoia, and phobias, and later hallucinations, dementia, and ultimately death. If there's one thing all these prion diseases have in common, it's that they're progressive, untreatable, and always fatal, which seems crazy to me. Ultimately, what prions cause is a progressive deterioration of the nervous system. This occurs because these aggregates of prions, misfolded proteins, accumulate in the nervous tissue, ultimately causing the death of neurons and causing "holes" to form in the brain, giving it a spongy appearance. This is why prion diseases are called spongiform encephalopathies. However, the incubation period for prion diseases is relatively long, meaning that years can pass from the moment of infection until symptoms appear . But once symptoms appear, the disease progresses rapidly, causing brain damage and eventually death. Symptoms of these diseases, depending on the type, include seizures, dementia, ataxia (i.e., problems with balance and coordination), or behavioral changes and personality changes. But do you know the craziest thing of all? That everything I have told you is caused by a protein. A molecule capable of causing and transmitting lethal diseases. That is, if you think of an infection, what probably comes to mind is a bacteria, a virus, or a parasite, which are ultimately microscopic beings that infect other organisms to survive, replicate, or whatever. But even if we take the simplest of them all, a virus that is barely made up of DNA, a few proteins, and a capsid that surrounds everything, it is something tremendously more complex than a simple protein. And ultimately, infectious beings have DNA or RNA, that is, genetic instructions that “tell” them how to act. Well, if you were already surprised that a tiny bug called coronavirus was capable of paralyzing half the world, now stop and consider that a misfolded protein is capable of causing neurodegenerative diseases that inevitably end the life of the organism it infects. WOW. Well, I hope you enjoyed this video a lot. It was a more complex topic than I thought when it came to searching for information and summarizing (because I left out a lot of things that I wanted to get rid of so as not to confuse you even more), but in the end it was a real learning experience. This video's theme was chosen by my Patrons, who voted on which of several themes would be the next video's theme. If you'd also like to be able to choose topics for future videos, and have access to exclusive content like anecdotes or reading recommendations, remember that you can support this channel and its content on Patreon by becoming a channel ATP, a mitochondria, or a cell. Patreon has been very well received since I started it, so I wanted to give my heartfelt thanks for supporting this channel and allowing it to continue. Thank you so much for watching this video, and see you next time!