Author Topic: Neurological Disorders - May be Caused by Defective Calcium Metabolism  (Read 9321 times)

Stephen

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Re: Neurological Disorders - May be Caused by Defective Calcium Metabolism
« Reply #3 on: December 30, 2010, 01:22:33 AM »
Neurological Disorders Resembling Huntington’s Disease May be Caused by Defective Calcium Metabolism

Comments by J. C. Spencer

Deranged calcium signaling is caused by disruptive calcium flow within nerve cells. Cell-to-cell communication and intra-cellular communication is the cause for neurodegenerative diseases. Abnormal calcium release is toxic to cells and results in impaired motor function, said Dr. Ilya Bezprozvanny, professor of physiology at UT Southwestern and senior author of the study published in the Nov. 26 issue of the Journal of Neuroscience.

I discuss defective calcium metabolism in my book Expand Your Mind - Improve Your Brain in Chapter 32 entitled Age well - He who finishes last, finishes well. Concerning calcium metabolism I state, “Usually the enzym calpain, which depends on calcium for its activity, keeps the buildup of protein down.  So, inadequate dietary calcium means that too much protein can build up because there is not enough calpain to keep the synapses clean.  Unfortunately, an excess of calcium in the diet also creates a problem because the calpain may start to interfere with proper neural transmissions.  Calpain can be an enemy of proper brain function when it is not regulated.  Proper calcium balance in the brain is vital.”

Moderation in all things produces better brain health and that includes proper intake of magnesium which serves as a calcium blocker when excess calcium is in the system.

Now for the article:

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“Deranged Calcium Signaling” Contributes to Neurological Disorder

Tue 25-Nov-2008

Newswise — Defective calcium metabolism in nerve cells may play a major role in a fatal genetic neurological disorder that resembles Huntington’s disease, researchers at UT Southwestern Medical Center have found in a mouse study.

The disease, called spinocerebellar ataxia 3 – also known as SCA3, or Machado-Joseph disease – is a genetic disorder that, like Huntington’s, impairs coordination, speech, and vision and causes brain atrophy. Although rare, the condition is one of the most common inherited forms of ataxia and most frequently affects people of Portuguese descent.

The UT Southwestern researchers previously had found that calcium flow within nerve cells is disrupted in Huntington’s disease. The latest findings, appearing in the Nov. 26 issue of the Journal of Neuroscience, suggest that SCA3, which is caused by a genetic defect similar to the one found in Huntington’s, involves the same “deranged calcium signaling,” researchers said.

Both SCA3 and Huntington’s are caused by repeating segments of DNA, although the repeats associated with each disease appear in different genes that code for different proteins. The genetic mutations cause repeated units of the amino acid glutamine to appear in the respective proteins. The more repeats there are, the earlier the onset of the disease.

In Huntington’s disease the mutated protein is Huntingtin; in SCA3 it is ataxin-3.

The researchers determined that the mutant human ataxin-3 activates a molecule that acts as a channel in the membrane of a sequestered chamber inside cells called the endoplasmic reticulum, or ER. The channel then releases calcium into the cell as a whole. Normal ataxin-3 did not activate the channel or cause calcium release.

The researchers also found that cells from a person with SCA3 showed abnormally high levels of calcium release when treated with bradykinin, a substance that also activates the calcium channel.

Such abnormal calcium release is toxic to cells and results in impaired motor function, said Dr. Ilya Bezprozvanny, professor of physiology at UT Southwestern and senior author of the study. “We’re generalizing the idea of calcium toxicity for this group of diseases, which are called polyglutamine expansion disorders,” he said.

The researchers also studied mice that had been genetically engineered to overexpress the human ataxin-3 protein containing excessive glutamine repeats. The mutant mice performed poorly on tests of motor coordination compared with normal mice and displayed age-dependent neuronal loss in the same brain regions that are affected in SCA3 patients.

To test whether blocking calcium release would alleviate symptoms in the mice, the researchers treated them for a year with dantrolene, a drug that blocks excessive calcium release from the ER in skeletal muscle cells. Dantrolene is approved for use in humans as a one-time emergency treatment for a reaction to anesthesia.

Treatment with dantrolene improved the coordination of the mutant mice and slowed brain atrophy.

Dantrolene is not suitable for long-term use in humans, however, because of side effects that can potentially harm the liver and the heart and cause neurological problems, said Dr. Bezprozvanny.

“The take-home message is not so much that dantrolene is the solution for treating SCA3, but that this shows a direction for research into a better drug to block similar targets with fewer side effects,” Dr. Bezprozvanny said.

The researchers now are studying whether blocking calcium release from the endoplasmic reticulum also can improve function in mouse models of Huntington’s and other neurodegenerative diseases such as spinocerebellar ataxia type 2 and Alzheimer’s disease.

Other UT Southwestern researchers involved in the study were Dr. Xi Chen, postdoctoral researcher in physiology; Dr. Tie-Shan Tang, instructor of physiology; Dr. Huiping Tu, former instructor of physiology; graduate student Omar Nelson; and Dr. Robert Hammer, professor of biochemistry. Researchers from Brunel University in London and RIKEN Brain Science Institute in Japan also participated.

The study was funded by the National Institutes of Health, the Robert A. Welch Foundation, the McKnight Endowment Fund for Neuroscience, the National Ataxia Foundation, Ataxia UK, Ataxia MJD Research Project Inc. and MEXT of Japan.

Dr. Ilya Bezprozvanny - http://www.utsouthwestern.edu/findfac/professional/0,2356,20034,00.html

UT Southwestern Medical Center



thanks for sharing valuable information for medical student really help me in my last article .again thanks.

kendersa

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Neurological Disorders - May be Caused by Defective Calcium Metabolism
« Reply #2 on: December 01, 2008, 04:07:01 PM »
I had wondered about this..........months ago I had asked the question about magnesium and HD
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Does anyone know if adding extra magnesium in HD patients would help the NMDA glutamate receptor function properly in the brain?  Since most patients who have HD eventually have about 93% of their NMDA glutamate receptor gone and have very low levels of magnesium-would adding large amounts of magnesium help make the calcium channel work properly in the brain cells and actually close them when necessary?  I know that people who have HD have very high levels of glutamate in their brain-so would adding the magnesium help the lock and key function of the NMDA receptor work better?
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We have started my brother on magnesium (non-synthetic) supplements.......have yet to find out how much he is actually supposed to take.....so I figured we would double the recommended usage.  I have read that it would probably take about 6 months for his magnesium levels to become normal so we shall see on the results month by month.  I have also debated on how to check and see if his magnesium levels are actually rising since I have read that your body can register normal levels of magnesium when in fact your brain's level of magnesium might be quite low.  Any help would be greatly appreciated    If anyone knows a great brand on magnesium supplements I would love to hear!
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.....its seems very interesting to me that symptoms of magnesium deficiency are quite similar to the physical symptoms of HD........and since magnesium is so depleted in patients with HD and used so extensively with HD for the NMDA glutamate receptor and as an antioxidant to deal with free radicals,wouldn't it be so great if adding magnesium could help deal with the physical aspects of HD

I have been trying to figure out if rats have a high amount of magnesium usually in their little bodies.  If they did, could that possibly be why scientists have not been able to replicate the physical symptoms of HD in them?  It would be so great if that really was the answer-a simple magnesium deficiency to negate the tremors, large gait, and muscle spasms that persist uncontrollably with those who have HD.  It would be so nice to just give my family extra magnesium to help be able to control their own bodies.
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Just wish they could tell me exactly how much Magnesium one should take if they have HD?  How much per day?  How often?  Which brand is the best?  Anyone?
« Last Edit: December 01, 2008, 04:10:06 PM by JC Spencer »

Offline JC Spencer

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Neurological Disorders - May be Caused by Defective Calcium Metabolism
« Reply #1 on: November 26, 2008, 10:05:06 PM »
Neurological Disorders Resembling Huntington’s Disease May be Caused by Defective Calcium Metabolism

Comments by J. C. Spencer

Deranged calcium signaling is caused by disruptive calcium flow within nerve cells. Cell-to-cell communication and intra-cellular communication is the cause for neurodegenerative diseases. Abnormal calcium release is toxic to cells and results in impaired motor function, said Dr. Ilya Bezprozvanny, professor of physiology at UT Southwestern and senior author of the study published in the Nov. 26 issue of the Journal of Neuroscience.

I discuss defective calcium metabolism in my book Expand Your Mind - Improve Your Brain in Chapter 32 entitled Age well - He who finishes last, finishes well. Concerning calcium metabolism I state, “Usually the enzym calpain, which depends on calcium for its activity, keeps the buildup of protein down.  So, inadequate dietary calcium means that too much protein can build up because there is not enough calpain to keep the synapses clean.  Unfortunately, an excess of calcium in the diet also creates a problem because the calpain may start to interfere with proper neural transmissions.  Calpain can be an enemy of proper brain function when it is not regulated.  Proper calcium balance in the brain is vital.”

Moderation in all things produces better brain health and that includes proper intake of magnesium which serves as a calcium blocker when excess calcium is in the system.

Now for the article:

- - - - - - - - - - - - - - -

“Deranged Calcium Signaling” Contributes to Neurological Disorder

Tue 25-Nov-2008

Newswise — Defective calcium metabolism in nerve cells may play a major role in a fatal genetic neurological disorder that resembles Huntington’s disease, researchers at UT Southwestern Medical Center have found in a mouse study.

The disease, called spinocerebellar ataxia 3 – also known as SCA3, or Machado-Joseph disease – is a genetic disorder that, like Huntington’s, impairs coordination, speech, and vision and causes brain atrophy. Although rare, the condition is one of the most common inherited forms of ataxia and most frequently affects people of Portuguese descent.

The UT Southwestern researchers previously had found that calcium flow within nerve cells is disrupted in Huntington’s disease. The latest findings, appearing in the Nov. 26 issue of the Journal of Neuroscience, suggest that SCA3, which is caused by a genetic defect similar to the one found in Huntington’s, involves the same “deranged calcium signaling,” researchers said.

Both SCA3 and Huntington’s are caused by repeating segments of DNA, although the repeats associated with each disease appear in different genes that code for different proteins. The genetic mutations cause repeated units of the amino acid glutamine to appear in the respective proteins. The more repeats there are, the earlier the onset of the disease.

In Huntington’s disease the mutated protein is Huntingtin; in SCA3 it is ataxin-3.

The researchers determined that the mutant human ataxin-3 activates a molecule that acts as a channel in the membrane of a sequestered chamber inside cells called the endoplasmic reticulum, or ER. The channel then releases calcium into the cell as a whole. Normal ataxin-3 did not activate the channel or cause calcium release.

The researchers also found that cells from a person with SCA3 showed abnormally high levels of calcium release when treated with bradykinin, a substance that also activates the calcium channel.

Such abnormal calcium release is toxic to cells and results in impaired motor function, said Dr. Ilya Bezprozvanny, professor of physiology at UT Southwestern and senior author of the study. “We’re generalizing the idea of calcium toxicity for this group of diseases, which are called polyglutamine expansion disorders,” he said.

The researchers also studied mice that had been genetically engineered to overexpress the human ataxin-3 protein containing excessive glutamine repeats. The mutant mice performed poorly on tests of motor coordination compared with normal mice and displayed age-dependent neuronal loss in the same brain regions that are affected in SCA3 patients.

To test whether blocking calcium release would alleviate symptoms in the mice, the researchers treated them for a year with dantrolene, a drug that blocks excessive calcium release from the ER in skeletal muscle cells. Dantrolene is approved for use in humans as a one-time emergency treatment for a reaction to anesthesia.

Treatment with dantrolene improved the coordination of the mutant mice and slowed brain atrophy.

Dantrolene is not suitable for long-term use in humans, however, because of side effects that can potentially harm the liver and the heart and cause neurological problems, said Dr. Bezprozvanny.

“The take-home message is not so much that dantrolene is the solution for treating SCA3, but that this shows a direction for research into a better drug to block similar targets with fewer side effects,” Dr. Bezprozvanny said.

The researchers now are studying whether blocking calcium release from the endoplasmic reticulum also can improve function in mouse models of Huntington’s and other neurodegenerative diseases such as spinocerebellar ataxia type 2 and Alzheimer’s disease.

Other UT Southwestern researchers involved in the study were Dr. Xi Chen, postdoctoral researcher in physiology; Dr. Tie-Shan Tang, instructor of physiology; Dr. Huiping Tu, former instructor of physiology; graduate student Omar Nelson; and Dr. Robert Hammer, professor of biochemistry. Researchers from Brunel University in London and RIKEN Brain Science Institute in Japan also participated.

The study was funded by the National Institutes of Health, the Robert A. Welch Foundation, the McKnight Endowment Fund for Neuroscience, the National Ataxia Foundation, Ataxia UK, Ataxia MJD Research Project Inc. and MEXT of Japan.

Dr. Ilya Bezprozvanny - http://www.utsouthwestern.edu/findfac/professional/0,2356,20034,00.html

UT Southwestern Medical Center

« Last Edit: November 26, 2008, 10:46:50 PM by JC Spencer »