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The researchers tested mice brains for the secret behind brain cell death.  (Source: Recognizing Deven)

The researchers found an important culprit in the cause of brain cell death -- a tumor killing preventing enzyme surpress AKT (pictured here), a critical protein to cell survival.  (Source: The Institute of Cancer Research)
Nature's kill switch seems to activate for some brain cells but not others, according to researchers

Preventing and reversing memory loss is a key field of research in the area of prolonging human life spans.  While humans are living much longer than they once did, many suffer from debilitating conditions such as Alzheimer's disease, which limit their quality of life during their later years.

Scientists at the University of Florida may have gained a significant insight into understanding what causes some brain cells to die, triggering these diseases, while others cells remain alive.  The studies, performed on mice examined two neighboring regions in the hippocampus; an anatomical region shaped something like a curved kidney bean.  The region is thought to be central to the formation of memories, and is one of the first regions affected by brain blood flow problems or Alzheimer's.

What researchers discovered was that the higher susceptibility to cell death in part of the hippocampus versus the other region was due to the enzyme PHLPP, pronounced "flip", silences the transcription of a gene that produces a critical protein to cell survival, AKT.  AKT inhibits many causes of cell death.  The inactivation in essence, amounts to the cell flipping its own kill switch.

Thomas C. Foster, Ph.D., the Evelyn F. McKnight chair for research on aging and memory at UF describes, "The question is why does one set of brain cells live and another set die when they are only millimeters apart in the same small brain structure?  We looked at an important signaling pathway that tells cells to stay alive or die, and the enzymes that regulate that pathway. Implicated in all this is a new protein that before a couple of years ago no one actually knew much about."

The conclusions were drawn by first finding AKT levels to be a key chemical difference between the living and dying cells.  From there, the cause of the AKT shortage was traced to high levels of the enzyme PHLPP1, the mouse version of PHLPP, an enzyme found in other mammals.  Ironically, the recently discovered enzyme suppresses tumors in many cases.  The compound was discovered by Alexandra Newton, Ph.D., a professor of pharmacology at the University of California, San Diego.

Professor Newton comments on the new research, stating, "Basically, PHLPP is important in controlling whether cells survive and proliferate or die.  If you want cells to survive brain disease, diabetes or heart disease, you want active AKT signaling and therefore low PHLPP. But if you want to stop cells that have the 'go' signal, like cancer cells, PHLPP can function as a brake. In this case, it appears as if there is an area in the hippocampus that is easily stressed and might undergo ischemia easily, because PHLPP is not allowing the AKT survival mechanism to work."

According to Professor Foster, the breakthrough could lead to new drugs to combat memory loss and brain damage.  He states, "Possibly, we have found a target that could be manipulated with drugs so that these brain cells can be saved from threats.  If one area of the hippocampus has a deficiency in cell-survival signaling, it is possible to find a way to ramp up the AKT protein. The caveat is, there are studies that show over-activating AKT may not be good for memory — AKT may be naturally lower in this region for an important reason. But in times of intense damage, there may be a therapeutic window to upregulate AKT and get some benefit to health."

It is still unknown why some regions of the brain flip the switch to trigger cell death, while others, which appear equally vulnerable to tumor formation, do not.

The research is published online in the Nature publication Cell Death & Differentiation.  



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RE: Hope
By MatthiasF on 12/12/2008 7:15:21 PM , Rating: 3
Should be mentioned that this article in Nature is complete bullshit science and it's release was meant to distract from the real cause of Alzheimer's disease discovered by a separate group.

http://www.physorg.com/news147971732.html

To paraphrase the article, samples were taken of the plaques that cause Alzheimer's and the DNA found inside was overwhelmingly (90%) the herpes simplex virus.

This is the second study done by the group that began to lead scientists away from genetics into environmental influences and it seems they were correct.


RE: Hope
By JonnyDough on 12/12/2008 10:31:56 PM , Rating: 2
You got rated down one. :-\ Although I think you may actually have a valid point.

HPV (of which there are over 100 types, several are defined within as a type of "herpes") have been known to cause all sorts of problems, many symptoms of which have yet to be discovered. We have a long way to go in understanding what HPV is and what it's doing to us. Some types of HPV can cause cancer of nearly any organ, this we know already.

My cat has a type of feline herpes which weakens her immune system but is non-transferable to humans.


RE: Hope
By MatthiasF on 12/13/2008 1:50:37 AM , Rating: 2
Yep, a majority of cancers are caused by some form of virus increasing cell defects either directly or indirectly in many ways.

As far as the rating down, it was my own fault. I used the S word and it auto rates down for filthy language.

Sorry to hear about your cat. My two dogs growing up as a child both had kidney damage that we believe was caused by HPV. Most humans are infected by some form of HPV and don't realize it (even the chaste), while some forms can be transferred between animals. Kind of made my guilty when I learned this, thinking we might have passed something off to them.


RE: Hope
By Gibsons on 12/13/2008 1:03:26 PM , Rating: 2
About 10-20 percent of human cancers are attributed to some sort of virus. There are always some other contributing factors as well, since not everyone who gets a particular virus gets cancer.


RE: Hope
By MatthiasF on 12/14/2008 5:06:33 PM , Rating: 2
I think the number of cancers directly attributed to viruses is closer to 30%, but I also stated indirectly.

Viruses and bacteria can still cause cell defects by stealing resources in areas where new cells are trying to grow, or even causing the body to attack itself in those regions.


RE: Hope
By William Gaatjes on 12/13/2008 5:18:19 AM , Rating: 2
I agree fully... When one lookes at how sophisticated cellular life is, one can not deny that an external factor must be of more importance then typical cell aging. Dna damage is so common that our cells are packed with genes and proteins to repair that damage or the cell will be killed. I do wonder if the cell has a killswitch because it is programmed to "live" or that the cell has a deadman button meaning that if anything goes wrong just completely shutdown. Why, since the most important rule is energy conservation in physics i believe the latter. Life must go on and cannot stop and therefore needs to be stopped when something goes wrong to prevent runaway actions compromising the collective of cells. In this case the body of a mouse... When does something go wrong ? Energetic elektromagnetic waves or particles disturb the internal machinery responsible for gene expression. Virusses use physics like all life to control this internal machinery, using electromagnetic energy or the typical behaviour of particles in elements. Each element has a specific behaviour and can be used like a program language when the rules are understood. Knowing that our bodies are pact with protection layers like a typical onion, i do believe that external factors are the cause of decay and in the end death... It is logical, since we have to share the planet with every living entity on it and share resources. From a certain point of view we are always defending and repairing. This we call healing something we do from the day we are born untill the day we depart... Since we still must obey the laws of nature, death is a natural thing. We use up energy and therefore we would die even when no external factors are accounted for. When dna is fully understood and all the rules of physics are perfectly known, We may rewrite our own dna to even overcome that obstacle. But would it be wise ? Only if we decide to swarm the universe, since time is not on our side.

There is once mentioned in a holy book that people would live to be very old. These people must have had perfect immune systems and better dna then people do now because those people had to live with other life as well.

At the moment we cannot make a live recording of what is going on in the body without disturbing the body. When we are capable of this, people will see that the body is invaded all the time by hostile life.


RE: Hope
By Gibsons on 12/13/2008 12:59:24 PM , Rating: 2
The article is in Cell Death and Differentiation and it's not "complete bull... science." You haven't even read it, have you?

FYI, Alzheimer's is mentioned once in the entire article, in the introduction. It's the following sentence:

"Studies on the human brain show that area CA1 of the hippocampus is one of the earliest brain regions to develop the pathological markers associated with Alzheimer’s disease,9 and the rodent models have correlated disease pathology to CA1 neuronal loss.10"

Now, you state the article is "complete bulls... science." Okay, what experimental errors did they make? Did they neglect any controls? Are any of their conclusions unwarranted from the data they present?

How do you know their motive was "to distract?" They found regional differences in the ability of some neurons ability to survive and may have found a mechanism underlying that difference. They made no claims regarding a cause for Alzheimer's.


RE: Hope
By MatthiasF on 12/14/2008 5:02:21 PM , Rating: 2
First of all, the study focused on the region of the brain used for creating memories (hippocampus). What other popular diseases revolve around memory?

Second of all, the logic behind the study is flawed. They're trying to prove that cell death is caused by a lack of a protein which can be reversed by using an enzyme that regulates it's creation. But why isn't the enzyme being created in these regions? Is it normal, a part of a cyclical process to make room in a tight region for new, fresh cells? Is it abnormal, caused by genetics, infection, etc.?

The study doesn't answer any helpful questions. It uses a lot of big words to report that a common cell process does indeed happen in this particular part of the brain and that some of the cells there are dying because of it.

The study organizers no doubt selected the region of the brain and the ease of proving their hypothesis to make some quick easy Alzheimer's research money.


RE: Hope
By Gibsons on 12/14/2008 6:35:35 PM , Rating: 2
Most of your questions are answered in the paper, so I'll assume you still haven't read it.

As for this comment: "Quick easy Alzheimer's research money." ha.

They did an enormous amount of work to get their data and showed a lot more than you seem to think. There are 8 figures in it, a few of which look to be months worth of work. Multiple repeats of some fairly difficult experiments. The results demonstrate a hell of a lot more than what's mentioned in the abstract or the blog post. Read the paper and find out for yourself. I'll warn you it's not an easy read.

Finally, if you think grant money is so easy to come by, apply for a grant yourself. You'll be rolling in grant money in no time, right?


RE: Hope
By michaelheath on 12/15/2008 1:10:51 AM , Rating: 2
I think it's irrational to call one study 'truth' and another 'bullshit' when we're still discovering how most of the human brain works. We're still figuring out how rats' brains work, and their CNS is significantly simpler than ours. A smart scientist would consider the possibility that there might be more than one contributing factor to a particular disease, or there's possibly many more undiscovered variances in human physiology that may affect who contracts Alzheimer's disease.

I suggest you re-read both articles, as it seems to me that neither is conclusive, seeing as how the words 'suggest' and 'likely' are used by both research teams. In fact, those who published their findings about HSV1 and Alzheimer's seems to be looking for more funding "...for further reaserch." They have a theory, and, like any scientist, they have to find out whether that theory has any merit. Progress has been made, but they're far from done.


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