Prion diseases are probably one of the most insane neurodegenerative diseases you will ever hear about. They transform the body’s own defenses against it after suddenly transforming into a silent saboteur. As these mutants spread cellular chaos through the brain, its functions slowly slip away. Starting with memory loss, to uncontrolled movements, and vision problems, and even difficulty with speaking, paired with shifts in personality. I don’t know about you guys, but that is wild to me. That one mutant protein can cause such a massive chain reaction.

And that brings us to the first official episode of axon!! Hi hello and welcome everyone!! If you guys haven’t watched the intro video for this podcast yet, which was the one right before this, I highly highly encourage yall to do so!! Anyways my name is Swarna and I will be your host. Before I get started, I wanted to quickly mention that the instagram for this podcast is axon_pod so make sure you go follow that so your are up to date with everything going on with the podcast! I also have a linktree on there that has extra resources and transcripts for the episodes as well as some other things just so y’all know if you wanted to access any of that. I’m also planning on putting out some extra fun content on the insta, hopefully soon, so make sure you follow so you won’t miss it! In this episode, we will be covering what prions are and the different types of neurodegenerative diseases that can be traced back to prion protein mutations. Then, we will go over different case studies of variations of prion diseases in humans, cows, deer, and sheep. The human case study is incredibly interesting, so make sure to stick around!

Alright! So, I thought we could start off by talking about why I chose to do this topic for the first episode. I’ll be honest, I am doing some research on prions outside of the podcast and that research really hooked me into neuroscience as a whole. I didn’t even set out to do the research, I was just having a conversation with one of my friends and it came up and I could not get it out of my brain. And now all of that has led to you listening to me talk about them on this podcast. It was just really astonishing how big of an impact these diseases have and how little we know about them. I hope that this episode piques your interest in prions and neurodegenerative diseases just as it did mine. And with that, let’s get into it!

First, let’s talk about what prions are! Prions proteins, or PrP (capital P, lower case r, and another capital P) are naturally occurring proteins present in the cells of various species, including humans. These proteins have 2 forms, a normal, harmless form which is the (PrP^C) and an abnormal, or misfolded form (PrP^Sc), which is the one that I like to think of as mutated. The mutated form of PrP is formed from the regular version by a posttranslational process, which we don’t know much about, resulting in the mis-folded configuration that is the main recognizable feature in the mutated version. ****I actually saw this concept in a paper I read while I was doing the research for this episode and I wanted to go over it with you all.

One really interesting thing it pointed out is that there are more than a dozen proteins can become prions by misfolding, so its not just PrP, but that is the protein that is most commonly associated with prions. Furthermore, a lot of diseases, not just the main ones in humans that we will be discussing today are actually traced back prions. Or, more accurately, there is more research supporting the idea that prions can cause neurodegenerative diseases like alzheimers, parkinsons, and others, but we aren’t completely sure because there are a lot of things we dont know about prions and the neurodegenerative diseases I just mentioned and the ones I will mention later on in the episode as well. With that being said, I highly recommend that those of you who are interesed in getting a deeper understanding of prions and neurodegeneration outside of the diseases we will go over today to go and read that paper because it has a ton of really cool information. I will have the paper linked on the extra resources page on my linktree so make sure to look at that!

Next, let’s get a deeper look into the types of prion diseases. In humans, a well-known one is Creutzfeldt-Jakob Disease, if I pronounced that correctly. It is commonly abbreviated as CJD so I will use that to avoid mispronunciation. CJD itself comes in several variations based on how it came to be, or what its source is. Sporadic CJD or sCJD arises spontaneously, which is where the s comes from. It has no known genetic or environmental contributing factors. This makes it really difficult to treat and cure it because we have no idea what started it in the first place. Next up, we have familial CJD or fCJD, which is associated with specific genetic mutations that run in the family, which is where the name comes from. And the final main one is acquired CJD which can result from exposure to contaminated tissues, like through medical procedures or consumption of infected meat. One way that’s causing a lot of fear is acquiring it by eating the beef of a cow with a prion disease. In cows it’s bovine spongiform encephalopathy, abbreviated as BSE and more commonly known as mad cow disease, which we will come back to later. Anyway, there are more subtypes of CJD based on clinical and pathological features, like iatrogenic CJD, caused by medical procedures. Quoting the NHS, “Iatrogenic CJD is where the infection is accidentally spread from someone with CJD through medical or surgical treatment. For example, a common cause of iatrogenic CJD in the past was growth hormone treatment using human pituitary growth hormones extracted from deceased individuals, some of whom were infected with CJD.” And we also have the rare Gerstmann-Sträussler-Scheinker syndrome. The merck manuals say that the Gerstmann-Sträussler-Scheinker disease is a prion disease that causes loss of coordination followed by slow deterioration of mental function. The disease is fatal, usually in about 5 years.” This one specifically is almost always inherited and is extremely rare. There is also some research connecting parkinsons and alzheimers to being prion diseases.

I also want to quickly mention another type of prion disease. Kuru is a rare and fatal neurodegenerative disorder. It was identified among the Fore people in Papua New Guinea and was associated with ritualistic cannibalism. The disease is caused by abnormal proteins called prions, which lead to brain damage. Symptoms include tremors, loss of coordination, and difficulty walking. Kuru is classified as a transmissible spongiform encephalopathy (TSE) and is related to other prion diseases like Creutzfeldt-Jakob disease. Since the decline of cannibalistic practices, kuru has become extremely rare. There is a really interesting paper I found from 2008 on a clinical study of kuru patients, which I will put in the episode resources if you are interested in looking further into that.

Moving on to what I think is the most interesting part, symptoms of prion diseases. If we look specifically at CJD, symptoms include rapid cognitive decline, personality changes, and neurological abnormalities like muscle stiffness and difficulty with coordination. From this information, we can actually narrow in on which parts of the brain the prion diseases are affecting. As written in a review article on the frontiers in neurology on the 25th of February in 2021, CJD is a rare neurodegenerative disease caused by accumulated misfolded proteins, which is the PrPsc we discussed earlier, with their deposition in the cortex, striatum, and thalamus. So if we are connecting these symptoms to the brain regions I just mentioned, we can get a better idea of where these symptoms are originating from, but keep in mind that it is not completely accurate. Cognitive decline can be associated with all three of the brain regions i mentioned before, but it’s important to note that cognitive decline often involves the hippocampus, frontal lobes, and other areas associated with memory and executive function. For context, executive function essentially means things like problem-solving, planning, decision-making, working memory, attention control, and the ability to switch between tasks. So, basically things that help you organize information, prioritize tasks, and regulate their behavior to achieve goals effectively. Next up, we have personality changes, which can be traced back to damage in the frontal cortex, which is a part of the cerebral cortex. We understand that the frontal cortex is involved in personality expression as well as decision-making, and social behavior, which are often also linked to personality. Ok, then we have, muscle stiffness and difficulty with coordination. Also, akinesia is seen with prion diseases and I thought I would mention that along with some of the mobility changes that we’re discussing here. Akinesia is basically feeling frozen and stiff and being unable to move one's muscles according to an article on osmosis. I have also read that there is sometimes loss of control of muscles, which can lead to unwanted jerking movements, which is referred to using a term called myoclonus. Generally, myoclonus is a result of damage in the frontal and parietal lobes, which control voluntary movements and motor planning. Also side note, the entire process of making voluntary movement possible is a really interesting topic when you look at what the brain does specifically during all of that, so let me know if y’all want me to cover that in the future!

Okay so I also wanted to quickly touch on some symptoms of prion diseases in other animals, including cows, sheep, and deer.

Starting off with cows, the prion disease commonly seen in these adorable animals is referred to as mad cow disease. Scientifically, it is called bovine spongiform encephalopathy or BSE for short. Now lets get into the symptoms! According to the USDA website, cattle with BSE have degeneration of the nervous system. Some symptoms that may be displayed include increased nervousness or aggression, similar to the behavioral changes that we see in CJD. Additionally, abnormal posture and coordination issues may be observed in cattle with BSE. This is also similar to the akinesia we talked about in CJD as well as myoclonus so definitely drawing parallels between the 2. Other symptoms include decreased milk production, weight loss, and difficulty swallowing as the disease progresses. Similar to CJD, there is no treatment or vaccine to prevent is and the affected animal generally dies within 2 weeks to 6 months following the onset of symptoms. One interesting that I wanted to point out is that a lot of these BSE cases are concentrated in the UK with only a couple being from other countries. But, we will get more into outbreaks and cases shortly, so make sure to stick around for that!