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PARKINSN  February 1996, Week 3

PARKINSN February 1996, Week 3

Subject:

Faulty Wiring in Brains Powerhouses <MedNews V09 #09>

From:

John Cottingham <[log in to unmask]>

Reply-To:

Parkinson's Disease - Information Exchange Network <[log in to unmask]>

Date:

Mon, 19 Feb 1996 08:03:50 -0600

Content-Type:

text/plain

Parts/Attachments:

Parts/Attachments

text/plain (139 lines)

Faulty Wiring in Brain's Powerhouses
NCRR Reporter Nov/Dec 1995
 
 
Just as a computer receiving too much or too little power might
burn out or malfunction, the brain's relay stations called
neurons can shut down or lower their output if they don't receive
sufficient energy. Thinking along these lines, researchers
studying neurodegenerative diseases, such as Alzheimer's,
Huntington's, and Parkinson's, are considering the possibility
that some of the symptoms of these disorders might originate from
fundamental errors in the brain's power grid.
 
Within the last few years, Dr. Douglas C. Wallace and his
colleagues at Emory University School of Medicine in Atlanta,
Georgia, have found mutations, or changes, in the structure of
DNA in the brain's powerhouses known as mitochondria that might
help illuminate the causes of several debilitating diseases.
Their studies were conducted at Emory's Microchemical Analysis
Facility for Molecular Biology, with instrumentation purchased
through NCRR's Shared Instrumentation Grant (SIG) Program.
 
Mitochondria are small energy-producing structures present in the
cytoplasm of all cells in the body. The energy, contained in a
chemical compound called ATP, fuels numerous processes in the
brain as well as the rest of the body. Without ATP, the human
body's machinery would come to a grinding halt. Raw materials for
ATP production, such as glucose, must be imported from cytoplasm
by the mitochondria. But many required tools enzymes and RNA are
manufactured within the mitochondria, specified by mitochondrial
genes. By analyzing the DNA of those genes, the Georgia
scientists have found mutations that might be related to the
occurrence of some neurodegenerative diseases. Mitochondrial DNA
is different from the nuclear DNA that carries most of our genes.
Its function is also more affected by minor damage than is its
nuclear counterpart because it has a limited capacity for self-
repair. Mitochondrial DNA is inherited maternally, so potentially
damaging mutations may accumulate over many generations.
 
In a recent study Dr. Wallace and his colleagues found that the
mitochondrial DNA in the brains of 22 patients with Huntington's
disease was structurally different from the mitochondrial DNA of
25 age-matched control individuals. The brain tissues from the
frontal, occipital, and temporal cortical lobes and putamen were
obtained by autopsy. The researchers found that a particular
deletion mutation loss of 5,000 nucleotide pairs in the
double-stranded DNA was elevenfold more frequent in the temporal
lobes and fivefold more frequent in the frontal lobes of the
patients with Huntington's disease than in the controls. But in
the occipital lobe and putamen, the results were comparable in
patients and controls.
 
The researchers do not know why the mitochondrial gene mutation
was not seen in the occipital lobe or putamen. But they suggest
that these areas of the brain might have suffered greater losses
of neurons and consequently greater loss of DNA during the
progression of the disease than the temporal lobes and cortex. As
a consequence, the DNA deletion levels might normalize in these
brain areas during the terminal stages of the disease, they say.
Dr. Wallace notes that the primary symptoms of Huntington's
disease (movement disorders and dementia) are caused by
malfunctioning basal cell ganglia, located in the putamen, where
a large proportion of cells may be lost. In contrast, more cells
in the other two brain areas survive during disease progression
and can display the high degree of mitochondrial DNA mutation.
 
Scientists' interest in mitochondrial mutations date back to
1988, when the Emory researchers detected a particular mutation
in mitochondrial DNA that was associated with an eye disease
known as Leber's hereditary optic neuropathy. Since that finding,
mitochondrial DNA mutations have been shown to be involved in a
host of degenerative diseases, ranging from blindness, heart
disease, and diabetes to movement disorders and dementia.
 
Dr. Wallace's detection of mitochondrial DNA mutations in
patients with Huntington's disease came on the heels of similar
findings in the brains of Alzheimer patients. The investigators
also discovered that a single nucleotide change was present in a
particular gene in approximately 5 percent of 173 Alzheimer
patients but only in 0.7 percent of the general population.
Researchers at the University of California, Los Angeles,
recently reported that they too had found the same mutation in
8.3 percent of 72 patients with Alzheimer's disease but in only
0.34 percent of 296 age-matched controls. Nevertheless, other
scientists have been unable to confirm the high mutation rates in
Alzheimer patients. "I think our work is valid, but there have
not been enough independent trials that have reproduced the
results and pinned them down completely," says Dr. Wallace.
 
In addition to limiting the supply of ATP, mitochondrial
mutations might also result in production of a type of toxic
substance called oxygen free radicals. These compounds can damage
DNA and cause extensive havoc in sensitive neurons.
 
Dr. Wallace and his colleagues have not yet been able to prove a
direct cause-effect relationship between a mitochondrial DNA
mutation and the symptoms of Alzheimer's or Huntington's disease.
But in dystonia muscle rigidity associated with basal ganglia
damage their DNA sequencing studies led them to one particular
mitochondrial DNA mutation that was handed down from mother to
daughter through several generations. "Dystonia is remarkably
similar to Huntington's or Parkinson's diseases. It just occurs a
little earlier," Dr. Wallace says. "While Huntington's disease is
inherited through a nuclear gene, we now show an inherited
mitochondrial DNA mutation for dystonia, which is absolutely
unequivocal.
 
"Our data say that movement disorders can be due to mutations in
mitochondrial DNA. They provide a superb foundation from which to
move out to the next level, which is the Alzheimer's mutation."
 
Ole Henriksen, Ph.D. and Alan G. Morton
 
The studies described in this article were supported by a
National Center for Research Resources Shared Instrumentation
Grant; the National Institute on Aging; the National Institute of
Neurological Disorders and Stroke; the National Heart, Lung, and
Blood Institute; and the Muscular Dystrophy Foundation.
 
Additional Reading
 
  1. Horton, T. M., Graham, B. H., Corral-Debrinski, M., et al.,
Marked increase in mitochondrial DNA deletion levels in the
cerebral cortex of Huntington's disease patients. Neurology, in
press.
 
  2. Johns, D. R., Mitochondrial DNA and disease, New England
Journal of Medicine 333:638-644, 1995.
---
Internet : [log in to unmask]
Telephone: +1-602-860-1121
FAX      : +1-602-451-1165
Web      : http://www.stat.com/~david
 
John Cottingham    "The parkinsn list brings Knowledge, Comfort, Hope, and
Homeboy             Friendship to the parkinsonian world."
LibraryH            Parkinson's Chat on the Undernet 8:30 PM CST -6 Daily.
                    If you access the Internet through a provider with a
[log in to unmask]     PPP/SLIP account, free IRC chat software is available. WFD

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January 2004, Week 4
January 2004, Week 3
January 2004, Week 2
January 2004, Week 1
December 2003, Week 5
December 2003, Week 4
December 2003, Week 3
December 2003, Week 2
December 2003, Week 1
November 2003, Week 5
November 2003, Week 4
November 2003, Week 3
November 2003, Week 2
November 2003, Week 1
October 2003, Week 5
October 2003, Week 4
October 2003, Week 3
October 2003, Week 2
October 2003, Week 1
September 2003, Week 5
September 2003, Week 4
September 2003, Week 3
September 2003, Week 2
September 2003, Week 1
August 2003, Week 5
August 2003, Week 4
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August 2003, Week 1
July 2003, Week 5
July 2003, Week 4
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July 2003, Week 1
June 2003, Week 5
June 2003, Week 4
June 2003, Week 3
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June 2003, Week 1
May 2003, Week 5
May 2003, Week 4
May 2003, Week 3
May 2003, Week 2
May 2003, Week 1
April 2003, Week 5
April 2003, Week 4
April 2003, Week 3
April 2003, Week 2
April 2003, Week 1
March 2003, Week 5
March 2003, Week 4
March 2003, Week 3
March 2003, Week 2
March 2003, Week 1
February 2003, Week 4
February 2003, Week 3
February 2003, Week 2
February 2003, Week 1
January 2003, Week 5
January 2003, Week 4
January 2003, Week 3
January 2003, Week 2
January 2003, Week 1
December 2002, Week 5
December 2002, Week 4
December 2002, Week 3
December 2002, Week 2
December 2002, Week 1
November 2002, Week 5
November 2002, Week 4
November 2002, Week 3
November 2002, Week 2
November 2002, Week 1
October 2002, Week 5
October 2002, Week 4
October 2002, Week 3
October 2002, Week 2
October 2002, Week 1
September 2002, Week 5
September 2002, Week 4
September 2002, Week 3
September 2002, Week 2
September 2002, Week 1
August 2002, Week 5
August 2002, Week 4
August 2002, Week 3
August 2002, Week 2
August 2002, Week 1
July 2002, Week 5
July 2002, Week 4
July 2002, Week 3
July 2002, Week 2
July 2002, Week 1
June 2002, Week 5
June 2002, Week 4
June 2002, Week 3
June 2002, Week 2
June 2002, Week 1
May 2002, Week 5
May 2002, Week 4
May 2002, Week 3
May 2002, Week 2
May 2002, Week 1
April 2002, Week 5
April 2002, Week 4
April 2002, Week 3
April 2002, Week 2
April 2002, Week 1
March 2002, Week 5
March 2002, Week 4
March 2002, Week 3
March 2002, Week 2
March 2002, Week 1
February 2002, Week 4
February 2002, Week 3
February 2002, Week 2
February 2002, Week 1
January 2002, Week 5
January 2002, Week 4
January 2002, Week 3
January 2002, Week 2
January 2002, Week 1
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December 2001, Week 4
December 2001, Week 3
December 2001, Week 2
December 2001, Week 1
November 2001, Week 5
November 2001, Week 4
November 2001, Week 3
November 2001, Week 2
November 2001, Week 1
October 2001, Week 5
October 2001, Week 4
October 2001, Week 3
October 2001, Week 2
October 2001, Week 1
September 2001, Week 5
September 2001, Week 4
September 2001, Week 3
September 2001, Week 2
September 2001, Week 1
August 2001, Week 5
August 2001, Week 4
August 2001, Week 3
August 2001, Week 2
August 2001, Week 1
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July 2001, Week 3
July 2001, Week 2
July 2001, Week 1
June 2001, Week 5
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June 2001, Week 3
June 2001, Week 2
June 2001, Week 1
May 2001, Week 5
May 2001, Week 4
May 2001, Week 3
May 2001, Week 2
May 2001, Week 1
April 2001, Week 5
April 2001, Week 4
April 2001, Week 3
April 2001, Week 2
April 2001, Week 1
March 2001, Week 5
March 2001, Week 4
March 2001, Week 3
March 2001, Week 2
March 2001, Week 1
February 2001, Week 4
February 2001, Week 3
February 2001, Week 2
February 2001, Week 1
January 2001, Week 5
January 2001, Week 4
January 2001, Week 3
January 2001, Week 2
January 2001, Week 1
December 2000, Week 5
December 2000, Week 4
December 2000, Week 3
December 2000, Week 2
December 2000, Week 1
November 2000, Week 5
November 2000, Week 4
November 2000, Week 3
November 2000, Week 2
November 2000, Week 1
October 2000, Week 5
October 2000, Week 4
October 2000, Week 3
October 2000, Week 2
October 2000, Week 1
September 2000, Week 5
September 2000, Week 4
September 2000, Week 3
September 2000, Week 2
September 2000, Week 1
August 2000, Week 5
August 2000, Week 4
August 2000, Week 3
August 2000, Week 2
August 2000, Week 1
July 2000, Week 5
July 2000, Week 4
July 2000, Week 3
July 2000, Week 2
July 2000, Week 1
June 2000, Week 5
June 2000, Week 4
June 2000, Week 3
June 2000, Week 2
June 2000, Week 1
May 2000, Week 5
May 2000, Week 4
May 2000, Week 3
May 2000, Week 2
May 2000, Week 1
April 2000, Week 5
April 2000, Week 4
April 2000, Week 3
April 2000, Week 2
April 2000, Week 1
March 2000, Week 5
March 2000, Week 4
March 2000, Week 3
March 2000, Week 2
March 2000, Week 1
February 2000, Week 5
February 2000, Week 4
February 2000, Week 3
February 2000, Week 2
February 2000, Week 1
January 2000, Week 5
January 2000, Week 4
January 2000, Week 3
January 2000, Week 2
January 2000, Week 1
December 1999, Week 5
December 1999, Week 4
December 1999, Week 3
December 1999, Week 2
December 1999, Week 1
November 1999, Week 5
November 1999, Week 4
November 1999, Week 3
November 1999, Week 2
November 1999, Week 1
October 1999, Week 5
October 1999, Week 4
October 1999, Week 3
October 1999, Week 2
October 1999, Week 1
September 1999, Week 5
September 1999, Week 4
September 1999, Week 3
September 1999, Week 2
September 1999, Week 1
August 1999, Week 5
August 1999, Week 4
August 1999, Week 3
August 1999, Week 2
August 1999, Week 1
July 1999, Week 5
July 1999, Week 4
July 1999, Week 3
July 1999, Week 2
July 1999, Week 1
June 1999, Week 5
June 1999, Week 4
June 1999, Week 3
June 1999, Week 2
June 1999, Week 1
May 1999, Week 5
May 1999, Week 4
May 1999, Week 3
May 1999, Week 2
May 1999, Week 1
April 1999, Week 5
April 1999, Week 4
April 1999, Week 3
April 1999, Week 2
April 1999, Week 1
March 1999, Week 5
March 1999, Week 4
March 1999, Week 3
March 1999, Week 2
March 1999, Week 1
February 1999, Week 4
February 1999, Week 3
February 1999, Week 2
February 1999, Week 1
January 1999, Week 5
January 1999, Week 4
January 1999, Week 3
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January 1999, Week 1
December 1998, Week 5
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November 1998, Week 3
November 1998, Week 2
November 1998, Week 1
October 1998, Week 5
October 1998, Week 4
October 1998, Week 3
October 1998, Week 2
October 1998, Week 1
September 1998, Week 5
September 1998, Week 4
September 1998, Week 3
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August 1998, Week 5
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August 1998, Week 1
July 1998, Week 5
July 1998, Week 4
July 1998, Week 3
July 1998, Week 2
July 1998, Week 1
June 1998, Week 5
June 1998, Week 4
June 1998, Week 3
June 1998, Week 2
June 1998, Week 1
May 1998, Week 5
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May 1998, Week 3
May 1998, Week 2
May 1998, Week 1
April 1998, Week 5
April 1998, Week 4
April 1998, Week 3
April 1998, Week 2
April 1998, Week 1
March 1998, Week 5
March 1998, Week 4
March 1998, Week 3
March 1998, Week 2
March 1998, Week 1
February 1998, Week 5
February 1998, Week 4
February 1998, Week 3
February 1998, Week 2
February 1998, Week 1
January 1998, Week 5
January 1998, Week 4
January 1998, Week 3
January 1998, Week 2
January 1998, Week 1
December 1997, Week 5
December 1997, Week 4
December 1997, Week 3
December 1997, Week 2
December 1997, Week 1
November 1997, Week 5
November 1997, Week 4
November 1997, Week 3
November 1997, Week 2
November 1997, Week 1
October 1997, Week 5
October 1997, Week 4
October 1997, Week 3
October 1997, Week 2
October 1997, Week 1
September 1997, Week 5
September 1997, Week 4
September 1997, Week 3
September 1997, Week 2
September 1997, Week 1
August 1997, Week 5
August 1997, Week 4
August 1997, Week 3
August 1997, Week 2
August 1997, Week 1
July 1997, Week 5
July 1997, Week 4
July 1997, Week 3
July 1997, Week 2
July 1997, Week 1
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June 1997, Week 4
June 1997, Week 3
June 1997, Week 2
June 1997, Week 1
May 1997, Week 5
May 1997, Week 4
May 1997, Week 3
May 1997, Week 2
May 1997, Week 1
April 1997, Week 5
April 1997, Week 4
April 1997, Week 3
April 1997, Week 2
April 1997, Week 1
March 1997, Week 5
March 1997, Week 4
March 1997, Week 3
March 1997, Week 2
March 1997, Week 1
February 1997, Week 5
February 1997, Week 4
February 1997, Week 3
February 1997, Week 2
February 1997, Week 1
January 1997, Week 5
January 1997, Week 4
January 1997, Week 3
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December 1996, Week 5
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December 1996, Week 3
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October 1996, Week 3
October 1996, Week 2
October 1996, Week 1
September 1996, Week 5
September 1996, Week 4
September 1996, Week 3
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April 1996, Week 3
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April 1996, Week 1
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March 1996, Week 3
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March 1996, Week 1
February 1996, Week 5
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February 1996, Week 3
February 1996, Week 2
February 1996, Week 1
January 1996, Week 5
January 1996, Week 4
January 1996, Week 3
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December 1995, Week 5
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July 1995, Week 2
July 1995, Week 1
June 1995, Week 5
June 1995, Week 4
June 1995, Week 3
June 1995, Week 2
June 1995, Week 1
May 1995, Week 5
May 1995, Week 4
May 1995, Week 3
May 1995, Week 2
May 1995, Week 1
April 1995, Week 5
April 1995, Week 4
April 1995, Week 3
April 1995, Week 2
April 1995, Week 1
March 1995, Week 5
March 1995, Week 4
March 1995, Week 3
March 1995, Week 2
March 1995, Week 1
February 1995, Week 4
February 1995, Week 3
February 1995, Week 2
February 1995, Week 1
January 1995, Week 5
January 1995, Week 4
January 1995, Week 3
January 1995, Week 2
January 1995, Week 1
December 1994, Week 5
December 1994, Week 4
December 1994, Week 3
December 1994, Week 2
December 1994, Week 1
November 1994, Week 5
November 1994, Week 4
November 1994, Week 3
November 1994, Week 2
November 1994, Week 1
October 1994, Week 5
October 1994, Week 4
October 1994, Week 3
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June 1994, Week 1
May 1994, Week 5
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May 1994, Week 3
May 1994, Week 2
May 1994, Week 1
April 1994, Week 5
April 1994, Week 4
April 1994, Week 3
April 1994, Week 2
April 1994, Week 1
March 1994, Week 5
March 1994, Week 4
March 1994, Week 3
March 1994, Week 2
March 1994, Week 1
February 1994, Week 4
February 1994, Week 3
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