Some Prions May Be Helpful

An anonymous reader writes "Sciencentral has an article saying that many prions, far from causing Creutzfeldt-Jakob Disease are actually responsible for long-term memory storage."

Comments

First ...um... something...

[Anonymous Coward]

"...actually responsible for long-term memory storage."

Not to mention all those cool Jedi powers.

Not my best work. I'm aiming for a Funny(2) or so.

Are prions really real?

[Anonymous Coward]

I thought that prions were something that not all scientists accepted as proven. Sort of like a 'theory'. Am I right on this?

Re:Are prions really real?

[Tango42]

You don't seem to know what a 'theory' is. All science is based on theory. Cells are a theory, gravity is a theory, hydrogen is a theory. So, of course, prions are a theory. How widely accepted the theory is, I don't know, but it's definately a theory.

Re:Are prions really real?

[smiths2]

Well, to be completely anal about this (this is slashdot, after all), cells and hydrogen are not theories. Cell theory describes how various eucaryote (sp?) life forms function on this planet, and hydrogen is simply an element with an atomic number of 1. A theory in science is not a "wild-assed guess." It is an explanation for the mechanism behind some natural phenomenom, backed up by large enough body of evidence that allows most scientists to grant it temporary assent. Part of that assent implies that it provides predictions for other phenomena that are later verified.

An hypothesis may eventually become a theory, once enough evidence supporting that hypothesis has been accumulated, but theories never become laws. The law of gravity is the F=G*m1*m1*m2*m2/(d*d) equation that you see in first semester physics class. The theory of gravity describes why the law is they way it is.

Re:Are prions really real?

[smiths2]

Ooooopss....that law of gravity should be
F=G*m1*m2/(d*d).
My bad.

Re:Are prions really real?

[reverseengineer]

Well, the idea of prions themselves is not really in dispute in the scientific community, as they can be isolated, and crystal structures do indeed suggest that some proteins, like PrP (just stands for Prion Protein) can assume a radically different conformation. The evidence that prions are involved somehow in certain degenerative neurological diseases is also quite strong, but the controversy lies in the fact that the evidence to this point is circumstantial. Specifically, few scientists would argue that misfolded proteins are involved in the pathology of diseases like kuru, CJD, and fatal familial insomnia, but the question of whether they are the actual cause or merely among the symptoms (this same issue also concerns the role amyloid plaques play in Alzheimer's) has not been answered to everyone's satisfaction, despite the efforts of Stan Prusiner and company.

Before Prusiner put forth his prion theory, slow acting viruses were thought to be responsible for infectious neurodegenerative diseases like kuru and scrapie. Prusiner demonstrated, however, that an extract of brain matter from a scrapie-infected animal, treated so as to disrupt nucleic acids but not denature proteins (thus eliminating bacteria and viruses as possible infectious agents) if injected in a healthy animal, could produce a scrapie-like disease in it. Thus, it was concluded that protein itself could act as an infectious agent. The mechanism by which this occurs is still not known for certain (hence, controversy), but the general theoretical outline is that an ingested prion is taken up by neurons, which do not recognize it as a dangerous foreign entity because they have the normal of the protein on their surface already, and incorrectly assume the prion to be more of the same. The misfolded prion protein has two fatal qualities: it can induce normal prion proteins on the neuron to flip themselves to the alternate misfolded form, and it's darn near indestructible. In particular, one theory about how prions specifically cause damage is that once your neurons realize they now have all this useless prion protein floating around, they target it for degradation in the lysosomes, cell organelles that contain an acidic pH and enzymes that catalyze protein breakdown. Unfortunately, the misfolded form seems to be highly resistant to acidic conditions and degradation by proteases (and coincidentally very heat tolerant- they withstand meat cooking temperatures, and even autoclaving), so prions clog up the lysosomes and cause them to burst, killing the neuron and spreading prions to other neurons. The destruction of neurons adds up to produce holes in the brain, giving the spongiform appearance characteristic of the disease.

There are some unanswered questions regarding the infectious nature of prions, including whether they are able to induce other prions to change conformation themselves versus receiving help from other proteins, and the role normal, healthy form prions play in the cell (initial studies suggested it played no known role, and that individuals with the gene for prion production turned off were highly resistant to transmissible prion infections, but other studies suggest prions are necessary for normal neurological function). here are also questions surrounding the role genetics plays in the disease- until it was linked to prions, CJD was considered a genetic disease, and it is believed that some individuals possess a mutated form of the prion gene that makes them more susceptible to both naturally acquired and tainted beef acquired forms of CJD. Also, variants of the same protein, PrP, have been implicated in every known prion disorder- kuru, CJD, nvCJD, FFI, GSS, scrapie, BSE- and these, while having a general pattern of brain destruction, loss of motor coordination, and eventual horrible death, are very different dieases that a focused in different areas of the brain, have different symptoms, and work on drastically different timescales. How is one protein responsible for all of these, and what is responsible for the d

We have dynamic memory with refresh

[Anonymous Coward]

As a prion protein, CPEB exists in two different forms: a dominant and a recessive. What's more, the dominant, or active, form can tell the inactive form to change shape and become active. In other words, it gets to work as a custodian of memory storage. This cycle continues over and over in a nerve cell. "If CPEB didn't have the prionlike property, it wouldn't be self-perpetuating," says Kandel.

It sounds like refreshing dynamic RAM (but over a longer time frame) where the prion protein acts as a template to 'pass on' the memory to a fresh molecule. Sounds like there may be some fundamental limit to the number of 'refreshes' before the dementia or the metabolic side-effects cascade into Alzheimer's. Probably going to be the next lifespan limiter after cancer and heart disease are cured.

Re:We have dynamic memory with refresh

[Tango42]

To what extent do things like Alzheimer's cause death? They harm quality of life, certainly, but not being able to remember things is not fatal. (other than secondary things, like forgetting you can't fly)

Re:We have dynamic memory with refresh

[some guy I know]

To what extent do things like Alzheimer's cause death? They harm quality of life, certainly, but not being able to remember things is not fatal.

I would guess that it could be fatal if it were to damage those parts of the brain responsible for autonomous processes, e.g., breathing.
IANAMP (medical person), so I don't know whether it can actually do this.

Re:We have dynamic memory with refresh

[azav]

Forgetting how to feed yourself contributes to death.

Remember, we use our brain for things occasionally. Sometimes, they are important.

Not pretty to watch someone going down the tubes with Alzheimer's. Pretty harrowing actually watching someone become a shell.

Re:We have dynamic memory with refresh

[simonjester2424]

Without self, a human life becomes more like a vegtable life.

Re:We have dynamic memory with refresh

[chadjg]

Yeah, it could be. But from what i've seen a lot of Alzheimer's patients can be damn healthy old in every other respect. A couple of my grand parents lasted over 10 years with that disease. They were strong up to the end, to the point that the staff at the rest home had to be careful.

I personally have had to help transport some alzheimer's patients by ambulance and when they are panicked they have incredible physical strength.

This could be way off, but Alzheimer's doesn't really kill, at least not quickly. It just makes life a curse.

I hope this isn't terribibly crass, but finding a cure or at least a good treatment is important financially. These people are very expensive to take care of. I'd put it at a higher priority than most other "popular" diseases. If this prion research has anything to do with anything that might find a cure for Alzheimer's, we probably should fund it big time. We are doing so well at keeping old people barely alive that a great number of them will be touched by this disease.

You learn something every day...

[Tango42]

"oversized neurons--the largest in the animal kingdom--of sea slugs known as Aplysia."

I never would have guessed that a slug would have big neurons... does anyone have any idea why this would be? Do big neurons help, or hinder, brain activity?

Re:You learn something every day...

[dpbsmith]

Squids have giant axons, too--they were used for all the early studies of how neurons work because they're big enough to get electrode into.

The textbook theory is that molluscs did not evolved the myelin sheath. Without myelin sheaths, propagation speed is proportional to axon diameter. Thus molluscs that need rapid propagation speed do so by having big neurons.

Re:You learn something every day...

[Soko]

I never would have guessed that a slug would have big neurons... does anyone have any idea why this would be?

Well, lawyers do need to regurgitate a lot of legal precedent at judges. And how else would Darl remember all those millions of lines of code?

Soko

Re:You learn something every day...

[azav]

Looking for a human reason as to why a slug is, might be the wrong approach. Biological system development often acts like multiple programmable field gate arrays. What ends ends up working is what works and is what is passed on.

There is no human defined reason behind why it is. The system was not designed, it evolved.

Re:You learn something every day...

[Anonymous Coward]

Insightful!? The reason why is because evolution made it that way is Insightful!? It is because it is adds nothing to the subject.

You failed to understand the question. Humans aren't defining the reason why. Tango42 wants to know if a human has discovered the reason behind why it is. Or more succinctly, why did slugs evolve big neurons?

dpbsmith responded to this by describing the suspected environmental pressures that favored the selection of large axon diameters in molluscs. Now that is insightful.

Prions as autocatalytic chaperone proteins

[Salis]

Chaperones are proteins that help other proteins fold through protein-protein interactions. They're very common in mammalian cells and are also used as sensors for heat shock or other environmental stresses that cause widespread protein denaturing.

A prion is a protein that can induce a conformational change in the structure of a molecule of its own type. It's called an autocatalytic reaction.

So you might get something like
Prion-inactivated + Prion-activated --> 2 Prion-activated.

The hypthesis is that the fibers responsible for Alziehmers form as the prions become activated and polymerize. The fibers then disrupt the synapses between neurons.

My two bits.

escaped memories?

[dankjones]

Does this mean that a memory could escape my brain and infect other people's brains?

just guessing

[Anonymous Coward]

just guessing, but if you can score a i.q.
rate above 100 and if people tend to ignore you
chances are that you'll be fine in old age.

after all it's not just one brain, but many many
brains interacting daily. also alot of information
is just "spread" acrose many brains (languages,
common knowledge, feeling, etc.)

i don't think just by looking at someone you can
give him a brain sickness, but living in a certain
"sociaty" situation for a long time and
getting certain "wrong" views enforced daily
might just trigger a damaged brain.
i believe that we have a given set of insticts
like animals that we should not try to override
to stay healty (intistict!=primitive,
instict more like premonition ...)
-
there are proteins, which have subsets of prions
and enzymes ... maybe pinapple helps with brain
damage?

Not everything is theory...

[Anonymous Coward]

...there are some things that we do know with certainty.

Re:Not everything is theory...

[Tango42]

Not in science. Maths has proof, so theorems are known with certainty, but there is not scientific equivilent.