Prions – Transmissible Spongiform Encephalopathy

00:01 And, finally, let's get to prion disease.

00:03 This is going to be a protein, not a microorganism, but an infectious protein, think about that for a minute, that is responsible for spongiform encephalopathy.

00:14 And it's called spongiform encephalopathy because the brain develops vacuoles where neurons have died and it looks like Swiss cheese at the end, which, you can imagine is probably not compatible with life.

00:27 So, what is happening in prion disease? So there is a normal, we all have, in every cell of our body, actually, but especially in the brain, we have prion proteins that are membrane proteins.

00:42 We don't know what they do, but we know that they are there, and they are usually in a normal stable conformation, that's that green rectangle that you see there, so that's the prion protein that's normal.

00:56 At a very, very, very low rate, that prion protein will get a kink in it, it will fold into another stable state that will be there now forever, but when it does that, that kinked form can now take more of the normal prion protein and convert it over to the dark side, so that you get more and more of the green rectangles becoming the kinked blue rectangles, and when you get enough of those, that aggregation of those prion proteins, causes neuronal death which gives you the spongiform encephalopathy.

01:38 This is Jakob-Creutzfeldt disease, this is mad cow disease, so this is a severe neurodegenerative process that is an infectious process.

01:52 What do you mean by infectious? Well, in fact what happened here is it had a spontaneous conversion which, fortunately, for all of us, happens at a very low rate, but you can have mutated forms of the protein that are carried around by certain people, where it's a little bit easier to get that kinked blue version, so you can have inherited forms of the prion disease.

02:15 And they tend to get this dementin spongiform encephalopathy at a earlier age, in their 40s or 50s, as supposed to 80s or 90s.

02:25 And then, here's how we know it's infectious, it's transmissible.

02:30 Because every now and then, you can, through surgical procedures or in the case of the Kuru in Papua New Guinea, they were eating the brains of their deceased, of their family members who had died, and they were able, in those patients who had already developed prion disease, to transmit that, and all it takes is one bad blue kinked prion and we're off and running.

03:00 It will take a little while, but you'll eventually develop spongiform encephalopathy and it's transmissible.

03:05 You can do it with surgical instrument, you can do it with ingestion, which was the case with mad cow disease.

03:11 So what is this about? So, it's a prion transmission, it's called the proteinaceous infectious particle, so if you're actually paying attention, you would say, gee, we'll I will call this proin not prion.

03:22 Well, proin was hard to say so they decided to call it prion. True story.

03:27 Okay. And, it is a conformational change of a normal small 27 kilo Dalton protein.

03:34 It typically has a very long latency, so it takes a long time before you can accumulate enough of these malformed kinked proteins, but it is at the end, a very rapidly progressive dementia, it's kinda like crystallization.

03:50 So early on, as you're making rock candy, or you're trying to crystallize something, it takes a long time to get it started, but once it get started it goes, that's kind of what happens here, so that we have a long latency and then finally a rapidly progressive dementia.

04:05 As I said they are spontaneous forms, every now and then, one of those prion protein kinks.

04:10 Or they're familial forms where they have mutations that allow the kinking to occur slightly easier, or they're infectious forms of the disease.

04:19 And, ultimately, we have neuronal vacuolization with extracellular plaques of the prion that's what's being shown there in the bottom panel.

04:28 The upper panel is just showing you the vacuolization that is characteristic and why we call it spongiform, it's spongy encephalopathy.

04:37 And with that, we had a tour through the entire microbial phylogeny, and hopefully, you've taken away a few interesting tidbits.