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Science

Scientists 'Switch Off' Brain Cell Death In Mice 78

Posted by Soulskill
from the are-you-pondering-what-i'm-pondering dept.
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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Scientists 'Switch Off' Brain Cell Death In Mice

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  • by SirGarlon (845873) on Monday May 07, 2012 @12:17PM (#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!
  • Can we shutdown the defense mechanism, clear out the prions, and turn back on the defense mechanism before the brain cells die?
    • by Ameryll (2390886)
      I assume we would have to - as there are many diseases out there where the sole problem is the build up of something bad.
    • by X0563511 (793323)

      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.

    • by sjames (1099)

      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.

      • by g0bshiTe (596213)
        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.
  • by virgnarus (1949790) on Monday May 07, 2012 @12:20PM (#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?

    • by sideslash (1865434) on Monday May 07, 2012 @12:22PM (#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?

      • by jeffmeden (135043)

        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"?

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

          • by jeffmeden (135043)

            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.

            • by mcgrew (92797) *

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

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

            • 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.

        • 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.

      • 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.
    • 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.

    • by girlintraining (1395911) on Monday May 07, 2012 @12:28PM (#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.

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

      • 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]

    • 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.

    • by jdavidb (449077) on Monday May 07, 2012 @03:08PM (#39919137) Homepage Journal

      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.

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

    • by sjames (1099)

      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... (Score:5, Interesting)

    by fuzzyfuzzyfungus (1223518) on Monday May 07, 2012 @12:21PM (#39917157) Journal
    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... (Score:5, Insightful)

      by ColdWetDog (752185) on Monday May 07, 2012 @12:37PM (#39917339) Homepage

      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.

    • by MrTester (860336)
      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 unc
  • I mean if we can treat the diesase, it'll be only slightly scarier than e-coli.

  • 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.

    • by Narcocide (102829)

      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.

      • by drfreak (303147)

        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

    • by ColdWetDog (752185) on Monday May 07, 2012 @12:45PM (#39917421) Homepage

      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.

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

  • by abrotman (323016)

    Was one of the mice named Jonathan Brisby?

  • by 3seas (184403) on Monday May 07, 2012 @12:26PM (#39917231) Journal

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

  • by kiehlster (844523) on Monday May 07, 2012 @01:06PM (#39917671) Homepage
    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.
  • >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?

    • by tmosley (996283)
      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.
  • Isn't that called "cancer"?

  • 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.
  • As long as I'm a mouse.

  • 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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