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Scientists 'Switch Off' Brain Cell Death In Mice

Soulskill posted more than 2 years ago | from the are-you-pondering-what-i'm-pondering dept.

Science 78

fishmike sends this excerpt from a Reuters report: "Scientists have figured out how to stop brain cell death in mice with brain disease and say their discovery deepens understanding of the mechanisms of human neurodegenerative diseases such as Alzheimer's and Parkinson's. British researchers writing in the journal Nature (abstract) said they had found a major pathway leading to brain cell death in mice with prion disease, the mouse equivalent of Creutzfeld-Jacob Disease (CJD). ... Mallucci's team found that the buildup of mis-folded proteins in the brains of mice with prion disease activated a natural defense mechanism in cells, which switches off the production of new proteins. This would normally switch back on again, the researchers explained, but in these ill mice the continued build-up of misshapen proteins keeps the switch turned off. This is the trigger point leading to brain cell death, because key proteins essential for cell survival are not made. By injecting a protein that blocks the "off" switch, the scientists were able to restore the production of the survival proteins and halt the neurodegeneration."

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I for one welcome our new rodent overlords (4, Interesting)

SirGarlon (845873) | more than 2 years ago | (#39917101)

First we had mice with enhanced brain development [slashdot.org] . Now, immortality! If those two research teams ever cross-breed their lab animals it will be like Hitchiker's Guide to the Galaxy!

Re:I for one welcome our new rodent overlords (4, Insightful)

BagOBones (574735) | more than 2 years ago | (#39917143)

I was thinking it is more like the plot to The Secret of NIMH [imdb.com]

Re:I for one welcome our new rodent overlords (4, Informative)

SirGarlon (845873) | more than 2 years ago | (#39917397)

Yeah, I thought of that too. :-) Slightly off-topic, but you should check out the book [wikipedia.org] ; I think it is considerably better than the movie.

Re:I for one welcome our new rodent overlords (1)

shiftless (410350) | more than 2 years ago | (#39922897)

I LOVED this book as a kid. Great plot and storyline.

Re:I for one welcome our new rodent overlords (3, Interesting)

Loughla (2531696) | more than 2 years ago | (#39917877)

This is the second reference to the Secret of Nimh I've seen on /. today (damnit, I can't find the other one).

It's a bit unnerving. I feel like there will be an announcement about a remake before too long.

So help me, if there is, I'm done with this site.

Re:I for one welcome our new rodent overlords (1)

slacker001 (951666) | more than 2 years ago | (#39939993)

Yeah, because if they make a movie, that's Slashdot's fault. Makes complete sense.

Re:I for one welcome our new rodent overlords (1)

Loughla (2531696) | more than 2 years ago | (#39940131)

No, because of very subtle advertising, like many companies now employ on social sites such as this one?

This may help you understand. . . . [reference.com]

Re:I for one welcome our new rodent overlords (0)

Anonymous Coward | more than 2 years ago | (#39917369)

This is just animal cruelty, mice have rights! Come people get green and animal friendly.

Re:I for one welcome our new rodent overlords (-1)

Anonymous Coward | more than 2 years ago | (#39917517)

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Re:I for one welcome our new rodent overlords (0)

Anonymous Coward | more than 2 years ago | (#39918109)

" Now, immortality! "

I say let's drop the 't'.

Re:I for one welcome our new rodent overlords (0)

Anonymous Coward | more than 2 years ago | (#39918679)

Now, immoraliy?

don't leave the defense mechanism off too long... (1)

bityz (2011656) | more than 2 years ago | (#39917123)

Can we shutdown the defense mechanism, clear out the prions, and turn back on the defense mechanism before the brain cells die?

Re:don't leave the defense mechanism off too long. (1)

Ameryll (2390886) | more than 2 years ago | (#39917261)

I assume we would have to - as there are many diseases out there where the sole problem is the build up of something bad.

Re:don't leave the defense mechanism off too long. (1)

X0563511 (793323) | more than 2 years ago | (#39917717)

The trouble is those damn prions are exponential breeders. Unless shutting off the cell death stops the prions from interacting with the normal proteins, you are going to eventually have a brain swimming in the damn things.

Re:don't leave the defense mechanism off too long. (1)

sjames (1099) | more than 2 years ago | (#39923869)

So far, we don't know how to clean it out, but it seems we might buy some time by shutting the defense mechanism off for the instances where it does more harm than good.

Re:don't leave the defense mechanism off too long. (1)

g0bshiTe (596213) | more than 2 years ago | (#39929437)

I just want to know if the brain stem keeps going with only the base instincts intact and if it can be transmitted through bites, or if I'm just worrying too much.

There for a reason (2)

virgnarus (1949790) | more than 2 years ago | (#39917135)

I'm aware that the "off" switch is there for a reason, and forcing it to stay inactive is probably going to have some nasty side effects. Am I correct in this?

Pardon my lack of complete knowledge here. I'm just IT for a cancer genomics group that just picks up stuff here and there. So I'm a bit aware that there's several points in a pathway that can be blocked, with each causing its own share of symptoms. Just simply blocking the entire "off" switch - which I would assume is a pretty deep pathway - would probably cause as much harm as it would help, wouldn't it?

Re:There for a reason (4, Interesting)

sideslash (1865434) | more than 2 years ago | (#39917173)

It seems like cell immortality basically equals cancer elsewhere in the body. Maybe since brain cells are not orginarily regenerated, longevity won't cause a direct problem?

Re:There for a reason (1)

jeffmeden (135043) | more than 2 years ago | (#39917329)

It seems like cell immortality basically equals cancer elsewhere in the body. Maybe since brain cells are not orginarily regenerated, longevity won't cause a direct problem?

"orginarily"?

Re:orginarily (1)

TaoPhoenix (980487) | more than 2 years ago | (#39917593)

Yes, because we can debug syntax errors in any language that computers speak and none of the ones people speak.

Re:orginarily (0)

Anonymous Coward | more than 2 years ago | (#39917947)

Sometimes it's a valid critism, particularly when the misspelled word looks like several other words and it is difficult to guess the intended meaning from context.

Case in point:
I first thought the GP meant "originaly" then I thought maybe he meant "organicly". Both words kinda fit the sentence but seemed a little off. After a minute I then realized he meant 'ordinarily". At least I think he meant ordinarily.....really only sideslash know for sure....

Re:orginarily (1)

jeffmeden (135043) | more than 2 years ago | (#39918175)

Yes, because we can debug syntax errors in any language that computers speak and none of the ones people speak.

Only after reading it again an hour later does it seem like "ordinarily" is the intended word. That, and who doesn't use a spellchecker in their browser? I don't care about their/there/they're or similar typos that are easy to ignore by parsing phonetically but when a word just isn't right it would really help to have some error checking.

Re:orginarily (1)

mcgrew (92797) | more than 2 years ago | (#39919445)

That, and who doesn't use a spellchecker in their browser?

Those who are at work and forced to use IE7 or earlier.

Re:orginarily (1)

TheCouchPotatoFamine (628797) | more than 2 years ago | (#39920969)

or people who are making a comment, cooking spaghetti, talking on the phone, and DONT LIVE THEIR/THERE LIFE to get A+ in syntax from YOU.

give it up.

Re:There for a reason (1)

sideslash (1865434) | more than 2 years ago | (#39919969)

It was supposed to be "ordinarily". My bad. And I did it in Chrome with spell checking enabled, so I was just in too much of a hurry.

It's my impression that "brain cells are not ordinarily regenerated" because I had always heard that they were _never_ regenerated, until recently I read about scientists inducing brain cells to regenerate in animal studies; so it must be possible in some circumdtances.

Re:There for a reason (1)

Frank T. Lofaro Jr. (142215) | more than 2 years ago | (#39920915)

Exercise creates new brain cells.

Using Apple products kills them.

Re:There for a reason (2)

interkin3tic (1469267) | more than 2 years ago | (#39918397)

There's a lot of "pruning," where many brain cells die as the brain is being formed. The thinking, as far as I've heard, is that you want neurons that aren't properly connected to die off, or else you'll get chaos. A damaged neuron could also potentially be giving aberrant signals that could mess up the system as well.

Re:There for a reason (0)

Anonymous Coward | more than 2 years ago | (#39919079)

... unless some cell starts to replicate again through, say, some mutation. That's exactly how cancer in other tissues develop in the first place — immortality and loss of replication control.

Re:There for a reason (1)

ColdWetDog (752185) | more than 2 years ago | (#39917217)

Well yes, the switch isn't there just to make zombies (although it does suggest a mechanism). But identifying the switch at a molecular and / or genetic level allows one to start playing with it and work out the feedback mechanisms, etc. It's really unlikely that someone is going to find a drug that magically stops Alzheimer's or Prion disease simply by studying this one switch.

But I, for one, welcome our new hyper-intelligent, prion resistant, immortal rodentia overlords.

Re:There for a reason (3, Interesting)

girlintraining (1395911) | more than 2 years ago | (#39917257)

Pardon my lack of complete knowledge here. I'm just IT for a cancer genomics group that just picks up stuff here and there. So I'm a bit aware that there's several points in a pathway that can be blocked, with each causing its own share of symptoms. Just simply blocking the entire "off" switch - which I would assume is a pretty deep pathway - would probably cause as much harm as it would help, wouldn't it?

Well, the prions don't stop being manufactured... so basically, those proteins continue to be generated until the person dies, and possibly beyond then. They can't be sterilized by any method known short of nuking them... prions are damn near indestructible. And we're tinkering with inactivating the only biological mechanism to halt their spread in the population.

Re:There for a reason (1)

SteveFoerster (136027) | more than 2 years ago | (#39918407)

So basically it's the plot to the movie version of I Am Legend? Awesome.

Re:There for a reason (1)

LordLimecat (1103839) | more than 2 years ago | (#39920029)

Bleach and autoclaving appear to be effective on prions:
source [wikipedia.org]

The World Health Organization recommends any of the following three procedures for the sterilization of all heat-resistant surgical instruments to ensure that they are not contaminated with prions:

        Immerse in a pan containing 1N NaOH and heat in a gravity-displacement autoclave at 121C for 30 minutes; clean; rinse in water; and then perform routine sterilization processes.
        Immerse in 1N NaOH or sodium hypochlorite (20,000 parts per million available chlorine) for 1 hour; transfer instruments to water; heat in a gravity-displacement autoclave at 121C for 1 hour; clean; and then perform routine sterilization processes.
        Immerse in 1N NaOH or sodium hypochlorite (20,000 parts per million available chlorine) for 1 hour; remove and rinse in water, then transfer to an open pan and heat in a gravity-displacement (121C) or in a porous-load (134C) autoclave for 1 hour; clean; and then perform routine sterilization processes.[62]

Re:There for a reason (0)

Anonymous Coward | more than 2 years ago | (#39917913)

In all situations where apoptosis is interfered with you are also risking protecting cancer cells. Until we can clearly differentiate between cancerous cells and normal cells you'd best tread carefully.

Re:There for a reason (1)

Deep Esophagus (686515) | more than 2 years ago | (#39918831)

I'm aware that the "off" switch is there for a reason, and forcing it to stay inactive is probably going to have some nasty side effects. Am I correct in this?

If I had mod points I'd bump you up because that's exactly what i was going to say; instead I'll just post what is really just a cleverly worded "me too" by way of supporting you.

Re:There for a reason (0)

Anonymous Coward | more than 2 years ago | (#39918845)

Except this isn't interfering with the apoptosis process itself, it is more like putting some duct tape on the cover of the usual neuronal self-destruct switch.

But would it also affect astrocytes or glial cells, though? If it did, that's probably the nasty side effects you're thinking of (e.g., glioblastoma, etc).

Re:There for a reason (3, Insightful)

jdavidb (449077) | more than 2 years ago | (#39919137)

You solve one problem, you create more problems. Then you work on solving those.

Living past 30 created a whole mess of new health issues. Living past 50 created many more. Now many of us live to 80 and beyond, and we are dealing with new health problems like the degeneration of the brain, problems our forebears never had to face.

I for one am thrilled that we are faced with these problems, and it would be wonderful to see the list of problems that come up when neuron death is turned off to see if anyone can come up with a useful way of solving those problems.

Re:There for a reason (1)

Frank T. Lofaro Jr. (142215) | more than 2 years ago | (#39920853)

Seems plausible the side effects would mean more job security for you.

Re:There for a reason (1)

sjames (1099) | more than 2 years ago | (#39925371)

It seems that this is a regulatory mechanism in neurons gone awry due to the mis-folded proteins. Jamming the mechanism probably does present problems of it's own, but many people would rather live normally for 5 years then die of the treatment than live with declining brain function for 3 years.

Interesting... (5, Interesting)

fuzzyfuzzyfungus (1223518) | more than 2 years ago | (#39917157)

Any word, as yet, on what eventually happens to the cells thus saved from early death?

Obviously, having your neurons die isn't a win; but the buildup of malformed proteins that started the shutdown process is presumably still developing if you bring protein synthesis back online.

Are the malformed proteins not a serious issue, so long as the spurious shutdown signal is ignored, or do they eventually hose the cell as well?

Re:Interesting... (4, Insightful)

ColdWetDog (752185) | more than 2 years ago | (#39917339)

Any word, as yet, on what eventually happens to the cells thus saved from early death?

Hard to say. It's a complicated, limited, experimental model using a fairly aggressive prion (infection to death in 12 weeks) so ringing this out to the slower neurodegenerative diseases in humans is a bit of stretch and likely limited by a number of caveats. They did find a 'window' of ability to rescue the cells - after around 9 weeks the rescue didn't work. But it did increase 'survival' in the mice so it's possible that it would have a clinically useful improvement in other similar diseases (assuming lots of things).

Remember, Prion disease in humans tends to be a very slow process. Timing could well be reflected in different mechanisms. Or not. This is really just an opening wedge rather than a robust look into the process.

Re:Interesting... (1)

ColdWetDog (752185) | more than 2 years ago | (#39917365)

More caveats (come on Slashdot, allow unicode and editing ferchristsakes) - I just quickly scanned the article. It's not my field. Any mouse neurodevelopmental geneticists in the audience?

Re:Interesting... (5, Funny)

Daetrin (576516) | more than 2 years ago | (#39917707)

"Any mouse neurodevelopmental geneticists in the audience?"

Squeak! Squeak squeak squeak squeakums. Squeak squeak squeaker squeak!

Re:Interesting... (1)

ColdWetDog (752185) | more than 2 years ago | (#39919757)

Cat got your tongue?

Re:Interesting... (0)

Anonymous Coward | more than 2 years ago | (#39920091)

No, I think a dog got his tongue.

A cold and wet dog.

Re:Interesting... (1)

Trogre (513942) | more than 2 years ago | (#39949033)

The mice will see you now.

Re:Interesting... (1)

mattack2 (1165421) | more than 2 years ago | (#39921925)

Do we know why prion disease in humans is a slow process?

Doesn't BSE affect cows in a very short time? (Maybe it's related to the animal's normal life expectancy somehow?)

Re:Interesting... (1)

MrTester (860336) | more than 2 years ago | (#39918899)

It seems pretty obvious to me.
When cell production continues despite the buildup of these misfolded proteins more and more of these misfolded proteins build up in the brain until they essentially ARE the brain.
At this point the person gets an unstoppable craving for brains that are not full of misfolded proteins.
At the same time the treatment that caused the continuation of cell production becomes contagious via the spreading of bodily fluids such as saliva.

I suspect other side effects will involve slow uncoordinated movement and an urge to moan.

Mouseburgers on the menu again? (1)

Tekfactory (937086) | more than 2 years ago | (#39917165)

I mean if we can treat the diesase, it'll be only slightly scarier than e-coli.

I'm a bit out of the loop... (1)

MyLongNickName (822545) | more than 2 years ago | (#39917167)

Have prions been showed to be a/the cause of Alzheimers? I remember reading that it was theorized to be a cause, but hadn't heard confirmation.

Re:I'm a bit out of the loop... (1)

Narcocide (102829) | more than 2 years ago | (#39917409)

Yes, I believe I've also heard that it has been suggested that many different forms of dementia have historically been mis-diagnosed Creutzfeldt–Jakob disease incidents. I don't know that it was anything more than speculation though.

Re:I'm a bit out of the loop... (1)

drfreak (303147) | more than 2 years ago | (#39922909)

From what I understand, Creutzfeldt–Jakob has a long gestation period of years but once fully manifested the patient has months to live. At least, for the one person I knew who actually had the disease, that was how it went down. For alzheimers, I don't know about gestation but it seems the disease can last many years before full degeneration or death. Mad Cow (which is the more well-know term for Creutzfeldt–Jakob, not PC at all go figure) seems to be much more aggressive and quick to complete its job of killing the patient.

After checking out Wikipedia [wikipedia.org] , it seems there are a few variations and Mad Cow is actually a disease in itself which causes Creutzfeldt–Jakob, not the disease itself.

Re:I'm a bit out of the loop... (3, Informative)

ColdWetDog (752185) | more than 2 years ago | (#39917421)

It's complicated [scientificamerican.com]

tl;dr Maybe yes, maybe no. Likely there is something Prion like in Alzheimer's dementia. Cause or effect is uncertain. More research needed. Stay tuned.

They should do this with cats instead... (1)

TimMD909 (260285) | more than 2 years ago | (#39917175)

... so you could Photoshop "I haz brain cellz" at the bottom.

NIMH (1)

abrotman (323016) | more than 2 years ago | (#39917229)

Was one of the mice named Jonathan Brisby?

Algernon .... (1)

Ungrounded Lightning (62228) | more than 2 years ago | (#39923505)

Was one of the mice named Jonathan Brisby?

Algernon seems more apropos.

With all these mouse experiments... (2)

3seas (184403) | more than 2 years ago | (#39917231)

...you have to wonder... are they trying to make real the Bairn of Pinky and the Brain?

Re:With all these mouse experiments... (1)

3seas (184403) | more than 2 years ago | (#39917247)

Brain... damn'it ....B R A I N.

Re:With all these mouse experiments... (3, Funny)

boristdog (133725) | more than 2 years ago | (#39917301)

Uh-oh. Better get your prion buildup checked!

If it's easy to 'switch off' such diseases.. (0)

Anonymous Coward | more than 2 years ago | (#39917375)

How difficult is it to switch them on?

Re:If it's easy to 'switch off' such diseases.. (1)

a90Tj2P7 (1533853) | more than 2 years ago | (#39917673)

How difficult is it to switch them on?

It's as easy as flipping a...

Re:If it's easy to 'switch off' such diseases.. (1)

shiftless (410350) | more than 2 years ago | (#39922965)

As easy as turning your mom on

Zombie Apocalypse Averted! Maybe... (2)

kiehlster (844523) | more than 2 years ago | (#39917671)

Sounds like injecting this stuff into zombies could eliminate their craving for fresh brains. Either that or we've equivalently turned our own brains from dry cat food to premium canned cat food.

Politicians (1)

doesnothingwell (945891) | more than 2 years ago | (#39933915)

Lets test it on congress first then the rest of them.

i do not get the summary (1)

mapkinase (958129) | more than 2 years ago | (#39918009)

>buildup of mis-folded proteins in the brains of mice with prion disease activated a natural defense mechanism in cells, which switches off the production of new proteins

> but in these ill mice the continued build-up of misshapen proteins keeps the switch turned off. This is the trigger point leading to brain cell death, because key proteins essential for cell survival are not made

So instead of dying of lack of the protein, mice will die of misfolded proteins' sedimentation?

Re:i do not get the summary (1)

tmosley (996283) | more than 2 years ago | (#39918491)

I'm not expert in that field, but it seems to me that the reason for the switch to be shut off is temporary, but something about the misfolded proteins doesn't allow the switch to turn back on, even though it should.

Re:i do not get the summary (1)

mapkinase (958129) | more than 2 years ago | (#39925123)

The problem of misfolded proteins never goes away. It's a mutation.

Re:i do not get the summary (1)

tmosley (996283) | more than 2 years ago | (#39942343)

Not all misfolded proteins are prions.

Re:i do not get the summary (1)

mapkinase (958129) | more than 2 years ago | (#39943081)

I meant misfolded proteins of the kind that "infects" 3d structures of other proteins of the same kind.

wth a summary that makes sense?!?!? (0)

Anonymous Coward | more than 2 years ago | (#39919609)

What is Slashdot coming to?

Cells that don't die? (1)

Conspiracy_Of_Doves (236787) | more than 2 years ago | (#39918055)

Isn't that called "cancer"?

Re:Cells that don't die? (1)

marcosdumay (620877) | more than 2 years ago | (#39918403)

No, cancer also reproduces faster than it should.

The Opposite... (1)

connor4312 (2608277) | more than 2 years ago | (#39919273)

I think, rather than enhancing the brain with this discovery, it would be interesting to see if there are any diseases that mess with this gene that could possibly be fixed. For example, people with Parkingson's disease have a high buildup of a certain protein. This makes me wonder if there are related diseases that can be cured by "resetting" this gene.

mod 04 (-1)

Anonymous Coward | more than 2 years ago | (#39919399)

product, BSD's to them...then Reasons why anyone truth, for all with the work, or are about 7700/5 All servers. Coming so there are people More stable Said one FreeBSD Irc.easynews.com Of various BSD ops or any of the They are Come example, if you what they think is Chronic abuse of invited back again. over a quality shall we? OK! a fact: FreeBSD but now they're the numbers. The *BSD has lost more do and doing what faster, cheaper, is perhaps

In order to avoid ethical carges of cruelty ... (0)

Anonymous Coward | more than 2 years ago | (#39920013)

they first practised on Dick Cheney

My insurance company will cover it too (1)

gelfling (6534) | more than 2 years ago | (#39921673)

As long as I'm a mouse.

Ender's Shadow (1)

Tyrannosaur (2485772) | more than 2 years ago | (#39923805)

I was going to say that there's always a drawback that's worse than the thing you are trying to fix, otherwise evolution would have fixed it long ago.

But reading more, it seems they just fixed a degenerative disease. Which is not universal and not eradicated nearly as well by evolution. ok.

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