Anyone listen to Radio Lab? I have been enjoying it for awhile; today I was listening to a program on SLEEP which was excellent.
I have insomnia so I love learning about sleep - although the more I learn about how important it is the more I stress over not getting enough. :rolleyes:
My Mom died of CJD, a prion disease, which I don’t understand much about but I do know prions are proteins that fold “wrong” and start replicating like viruses. Which is super bad. that’s about as much as I know except what it’s like to watch someone live and die with it.
So part of the program I linked to talks about sleep being waves of “cleaning” in your brain, where messed up proteins get cleared out. So I thought, wonder if chronic sleep deprivation would be a risk factor for prion disease?
Not sure if it’s totally understood, but my recollection is that the vast majority of CJD cases are due to contaminated transplants or blood transfusions.
I don’t think that is true. it’s been seven years but I was told there are three kinds of CJD a person can have and my Mom’s was “sporadic” - they have no idea how people get it.
it may be you don’t have to “catch” it from anywhere - that your proteins can just “turn” for some reason. but that is a total guess on my part.
maybe I should have put this in GQ.
I do know there are many kinds of prion disease, and if anyone knows how you get them I’d like to know.
(aside from eating cows with BSE or elk with chronic wasting disease or any animal with it)
it could have been a lot worse - she was a very happy demented person and, although her balance was affected and she had falls, she never broke a bone.
it was like Alzheimer’s but much faster - just slightly over a year from the first symptoms to death.
once I got over the grief of knowing something terrible was wrong with her, we had some happy times. I got to take care of her through most of it and it was a privilege.
There are three forms of CJD - inherited, infectious, and sporadic. The names match how you get them: inherited is due to a mutation that passes from parent to child; infectious is caused by eating a prion, like with mad cow disease or kuru (vCJD); and sporadic means there’s no obvious cause. My understanding is that this is thought to be just tremendously bad luck - one protein misfolds by accident and triggers a chain reaction.
From what I know about the molecular biology of prions, I cannot imagine any way in which lack of sleep could predispose someone to get one. That said, there’s still a lot we don’t understand. But so far, as far as I know, no one has ever demonstrated a link between sleep deprivation and protein folding problems.
Fatal familial insomnia is a completely different disease, also caused by a prion. It’s fairly horrifying. As you reach middle age, you start having a harder and harder time sleeping, until eventually you can’t sleep at all. However, your need for sleep never decreases. You eventually die of basically being too tired and all that comes with it. Awful. There’s an interesting book about it called “The Family that Couldn’t Sleep”. It documents an Italian family that’s had it for centuries. There came to be quite a strong stigma attached to it. It was considered the family curse. IIRC, several people committed suicide when they started to have symptoms. And even in this day and age, when they were writing the book, many family members refused to openly acknowledge that the disease existed.
The part about rats is probably a reference to this article which I just happened to come across recently as I was interested in whether it was possible to reverse the epigenetic markers created by DNA methylation.
It seems that sleep deprived rats showed a decrease in methylation at sites associated with epigenetic markers - if I’m reading the paper correctly (big if there).
I was tipped off to this line of inquiry by recent reports that sleep deprivation caused the change in the activity of a large number of genes. It was so large that it seemed odd so on one of my many pointless excursions, I decided to investigate.
This probably has nothing to do with prion diseases although it’s not outside the realm of possibility. I’m not familiar enough with that research to say for sure, but as I understand it, prion protein has the same amino acid sequence as the normal version of the protein, but it’s folded incorrectly. IOW, the topology or 3D structure is different.
Proteins are sufficiently complex that it is often possible for them to have more than one stable configuration. It appears that somehow the normal version is corrupted into the prion configuration. That would be so bad except that in the new form, it seems to have the ability to cause correctly formed proteins to assume the aberrant form. I’m sure I’m missing a lot but I think that’s more or less accurate.
A few months ago I was conducting lit review for a project proposal I had regarding an Alzheimer’s therapeutic. I don’t remember which paper I read it in, but I distinctly recall someone making a connection between sleep deprivation and amyloid plaque buildup for the exact reason you mentioned; they hypothesized that degradation of misfolded amyloid B is accelerated during sleep. If you care enough I could try to dig it up again. Alzheimer’s is a protein aggregation disease which is similar to prion diseases, the key distinction being that amyloid B/tau in AD haven’t been shown to be transmissible like prions are.
From what I understand, prions catalyze the mis-folding of like proteins, by some mechanism that is not clear, but there is probably some additional chemical agent involved. In something like CJD, mis-folded proteins spread at an exponential rate: one mis-folded protein catalyzes the mis-folding of another, both of which go on to catalyze two more, the four of which, ad infinitum. It would seem that the chemical agent that facilitates the catalysis is a very important part of the picture: its abundance would govern the rate of prion propagation. My guess would be that prions are actually quite pervasive, but other aspects of biology govern whether one is actually susceptible to prion disease.
As far as prion-driven insomnia, I would put forth that sleep itself is primarily an electro-chemical response to the body’s production of natural sedatives, which bind to specific receptors in the brain. Receptors are protein structures in cell membranes, so if they become mis-folded, the chemicals that cause sleep cannot bind to them, hence sleep will simply not follow. In other words, prion-caused insomnia is probably not due to lack of sleep but due to whatever caused the receptors to mis-fold in the first place.
If you follow the links, you’ll find cites to the journal articles.
The first one is, as you may have noticed, from Stanley Prusiner. For people not familar, this is the intrepid fellow who championed the very concept of prions in the face of a substantial amount of incredulity from his peers.
Oh yeah, I wasn’t arguing against that (that was actually one of the articles I reviewed :)). If you get AB aggregates in your neurons, you’re probably in trouble. The transmission I’m referring to is via food/blood such as CJD/Kuru. AFAIK, that hasn’t been demonstrated in the Alzheimer’s system.
I did realize that. Sorry. I only posted it for the fact that there was some indication of similarities to prion diseases, not that there was any indication that Alzheimer’s is transmissible - thankfully. Although I couldn’t help wondering what would happen to a zombie that ate an infected brain. Demented zombie? But that’s probably redundant.
I was also wondering if you could really consider it a prion if there were good evidence that it wasn’t infectious. Although cannibals get Kuru by eating human brains so you have to wonder how far they’re willing to go test the theory. See, I didn’t get off on the zombie tangent for no reason (looks to see if anyone is buying that).
I work down the hall from a prion research lab, and I believe their work (and that of others) has shown pretty conclusively that RNA can act as a cofactor to promote prion formation. They think that any large, negatively charged molecule could do it, but that is still to be proven. Also, although RNA CAN do it, it’s not sure if it actually DOES do it in the body.
