Folks:
I have attached a newswire article for your consumption. Apparently
research now indicates that non-nuclear DNA in the mitochondria is
responsible for Parkinson's. If I remember correctly, mitochondrial DNA is
always inherited from the mother. I remember something about using this DNA
to trace humanity back to an "Eve" somewhere in Asia.
Also, NADH is a principal participant in the Complex I process.
Ron Reiner (48 + 1yr)
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U.Va./MitoKor Research Team Issues Report/ Genetic Defect May Point
to Heredity as a Source of Parkinson's Disease
Source: PR Newswire
CHARLOTTESVILLE, Va., Oct. 11 /PRNewswire/ via Individual Inc. -- A
specific genetic defect that may cause Parkinson's disease has been
identified by scientists at the University of Virginia and MitoKor, a
California-based biopharmaceutical company, according to a study
published in the October issue of the Annals of Neurology.
"There is a piece of DNA that doesn't play by the rules," said W.
Davis Parker, professor of neurology at U.Va. and leader of the
research team. "The genes contained on mitochondrial DNA (mtDNA) exist
independent of nuclear DNA. In other words, this is a new principle of
human genetics that may explain why some diseases currently thought of
as sporadic, like Parkinson's, may in fact be inherited in an
unorthodox way."
The scientists found that the genetic defect affects a mitochondrial
enzyme called complex I. Although scientists have suspected for the
past seven years that the complex I defect is a key factor in the
onset of Parkinson's, they did not know the origin of the defect. The
U.Va/MitoKor team found that the complex I defect arises from
mitochondrial DNA and interferes with the function of mitochondria --
thousands of thread-like bodies in each cell which contain enzymes for
the production of energy.
"Complex I, which is abnormal in Parkinson's patients, is a
bioenergetic enzyme that serves as the principal starting point of the
electron transport chain, the energy generating mechanism found in the
mitochondria of each cell," said Robert E. Davis, chief executive
officer of MitoKor and a co- author of the study. "We believed that a
mitochondrial rather than a nuclear genetic mechanism was at work in
Parkinson's."
To test the theory, the researchers developed proprietary cybrid
(cytoplasmic hybrid) cell lines to model the mitochondrial DNA of
Parkinson's patients. First, human neuroblastoma cells -- embryonic
cells derived from the neural tube that give rise to neurons -- were
depleted of all their mtDNA. Mitochondrial DNA from 24 Parkinson's
patients was then transferred into those cells, the resulting cell
lines were cultured. Cybrid cell lines possessing mtDNA from 28
non-Parkinson's patients were used as the normal controls.
The scientists then performed a series of biochemical assays on the
cybrid cell lines, measuring cytochrome oxidase activity and complex I
activity, the key elements within the mitochondrial electron transport
mechanism. They also analyzed for the production of oxygen radicals
and the effects of a parkinsonism-inducing toxin called MPTP, a
contaminant of an illegally prepared heroin-like narcotic.
Complex I activity was 20 percent lower in the Parkinson's disease
(PD) cybrids as compared to the controls.
Additional research demonstrated that the genetically encoded complex
I defect of Parkinson's disease serves as a source of oxygen radical
generation. Oxygen radicals are widely believed to play a role in the
death of neurons in neurodegenerative diseases like Parkinson's,
Alzheimer's and amyotrophic lateral sclerosis (ALS or Lou Gehrig's
disease).
Also, cells containing Parkinson mtDNA were more susceptible to an MPTP
derivative.
This indicates that even though the enzyme defect is genetic,
environmental toxins could still contribute to the disease's
development.
"While the genetically determined complex I defect in Parkinson's
disease may itself be sufficient to produce the disease, our research
does not rule out the importance of external toxins in the disease
process," said Dr. Russell Swerdlow, U.Va. neurologist and lead author
of the study.
"The observation that a specific biochemical defect can render cells
more vulnerable to MPTP toxicity illustrates how interactions between
an environmental mitochondrial toxin and an apparent mtDNA defect
could accelerate neurodegeneration. This may explain why some
individuals develop Parkinson's disease following toxin exposure,
while others similarly subjected to the same toxin at the same dose do
not."
The U.Va./MitoKor team's next step will be to characterize the exact
mtDNA mutations that may lead to Parkinson's disease. "We are
conducting further mutational analysis of the mtDNA of Parkinson's
disease patients," Davis said. "Once the defect or defects are known,
we'll be working to develop a therapeutic agent that reverses the
complex I defect."
MitoKor, a development-stage biopharmaceutical company in San Diego,
Calif., is the only company in the United States whose sole focus is
the role of mitochondria in human disease. Their proprietary
technology is leading the way in the commercialization of
pharmaceutical and diagnostic products targeted to treat Alzheimer's,
Parkinson's, diabetes mellitus (NIDDM) and schizophrenia. MitoKor was
formed in 1992 under the name Applied Genetics.
SOURCE MitoKor
/CONTACT: Marguerite Beck of U.Va., 804-924-1501; U.Va.'s TV News
Office, 804-924-7550; Linda Seaton for MitoKor, 619-455-5500/
