Continuing with the information flow...
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Mitochondrial function in Parkinson's disease. The Royal Kings and Queens
Parkinson's Disease Research Group.
Schapira AH; Mann VM; Cooper JM; Krige D; Jenner PJ; Marsden CD
Department of Neuroscience, Royal Free Hospital School of Medicine, London,
UK.
Ann Neurol 32 Suppl: S116-24 (1992)
Abstract
There is increasing evidence for a defect of mitochondrial respiratory
chain function in Parkinson's disease. Specific NADH CoQ1 reductase
(complex I) deficiency has been identified in the substantia nigra.
Available evidence suggests that this defect is confined to the substantia
nigra and is not present elsewhere in the parkinsonian brain. The absence
of a detectable mitochondrial abnormality in the substantia nigra of
patients with multiple system atrophy also suggests that the complex I
deficiency in Parkinson's disease is not simply due to an artifact of
neuronal degeneration. Evidence for abnormal mitochondrial function in
skeletal muscle is conflicting; two studies showed multiple respiratory
chain defects and one study was unable to demonstrate any deficiency. A
severe deficiency of complex I activity has been found in platelet
mitochondria from parkinsonian patients. This finding has not as yet been
confirmed. Platelet homogenates do not show the complex I deficiency,
however, suggesting that such a preparation may be too insensitive to
detect the defect. The role of complex I deficiency in the events that
culminate in dopaminergic cell death in Parkinson's disease remains
unresolved. It is likely that if this mitochondrial defect is confirmed, it
will be related to a number of other factors, including environmental
agents, oxidative stress, and genetic predisposition.
Mesh Headings
Cell Death
DNA, Mitochondrial
Electron Transport
Human
Mitochondria*
Mutation
NAD(P)H Dehydrogenase (Quinone)
Parkinson Disease*
Substantia Nigra
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Unique Identifier: 92378151
Chemical Identifiers (Names)
EC 1.6.99.2 (NAD(P)H Dehydrogenase (Quinone))
28289-54-5 (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
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Mitochondrial oxidative phosphorylation defects in Parkinson's disease.
Shoffner JM; Watts RL; Juncos JL; Torroni A; Wallace DC
Department of Neurology, Emory University School of Medicine, Atlanta, GA
30322.
Ann Neurol 30: 332-9 (1991)
Abstract
Parkinson's disease has been associated with defects in oxidative
phosphorylation (Oxphos). We analyzed mitochondria isolated from muscle
biopsies of 6 patients with Parkinson's disease for deficiencies in Oxphos
enzymes and for mutations in the mitochondrial DNA. Oxphos enzyme assays
were compared to the 5 to 95% confidence intervals from 16 control
subjects. Four patients had complex I defects, whereas 1 patient had a
complex IV defect. A genetic basis for Parkinson's disease was suggested by
the presence of affected relatives of 2 patients with Parkinson's disease.
Known pathological mitochondrial DNA mutations (insertion-deletions or
point mutations) were not found. We conclude that Parkinson's disease is a
systemic disorder of Oxphos, probably of a complex genetic etiology.
Premature cell death in the nigrostriatal dopamine pathway could be due to
energetic impairment and accentuated free radical generation caused by an
Oxphos defect.
Mesh Headings
Adult
Aged
Aging
Biopsy
Child
DNA, Mitochondrial
Female
Glycogen
Human
Lipids
Male
Middle Age
Mitochondria, Muscle*
Oxidative Phosphorylation*
Oxygen Consumption
Parkinson Disease*
Polymorphism (Genetics)
Support, Non-U.S. Gov't
Support, U.S. Gov't, Non-P.H.S.
Support, U.S. Gov't, P.H.S.
Unique Identifier: 92060883
Chemical Identifiers (Names)
(Lipids)
9005-79-2 (Glycogen)
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PCR analysis of platelet mtDNA: lack of specific changes in Parkinson's
disease.
Sandy MS; Langston JW; Smith MT; Di Monte DA
California Parkinson's Foundation, San Jose 95128.
Mov Disord 8: 74-82 (1993)
Abstract
An alteration within the mitochondrial DNA (mtDNA) has been hypothesized to
underlie the deficiencies in mitochondrial complex I activity observed in
the platelets, striatal muscle, and brain tissue of individuals with
Parkinson's disease. Here we utilized the polymerase chain reaction (PCR)
to analyze mtDNA obtained from the platelets of nonmedicated patients with
early Parkinson's disease (n = 8) and aged-matched controls (n = 6) for the
presence of deletion(s) or addition(s) equal to or greater than 50-100 base
pairs. Initial attention was focused upon detecting a 4.977 kb deletion
previously found in the brains of parkinsonian patients and some aged
controls. Indeed, a large deletion of approximately 5.0 kb was observed in
the platelet mtDNA from all parkinsonian individuals. However, this defect
was also found in all age-matched controls as well as in a group of young
healthy subjects (n = 5). In addition, we searched for the presence of
smaller changes in platelet mtDNA from parkinsonian patients by PCR
analysis of four mtDNA segments that code for seven of the complex I
polypeptides. No large deletions or additions were detected within these
four regions of mtDNA in any of the disease or age-matched control samples.
We conclude that (a) a 4.977 kb deletion is apparently present in a
subpopulation of platelet mtDNA from all individuals, and (b) no
macrosequence alteration in mtDNA is likely to underlie the deficiency in
complex I activity reported in platelet mitochondria from parkinsonian
patients.
Mesh Headings
Adult
Aged
Base Sequence
Blood Platelets*
Chromosome Deletion
DNA, Mitochondrial*
Gene Amplification
Human
Male
Middle Age
NAD(P)H Dehydrogenase (Quinone)
Parkinson Disease*
Polymerase Chain Reaction*
Support, Non-U.S. Gov't
Unique Identifier: 93125606
Chemical Identifiers (Names)
EC 1.6.99.2 (NAD(P)H Dehydrogenase (Quinone))
(DNA, Mitochondrial)
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I've hardly made a dent in the info available yet!! Even tho' I'd rather be
doing this research for something other than PD, in a way this is fun playing
detective. I intend to "solve" this case. I ABSOLUTELY REFUSE to accept the
dire predictions for PD. Basically my philosophy (or whatever you may call
it) is when I'm told what to do and/or how I have to do something, I simply do
the opposite (right or wrong, I can't help it). Some people believe that
people develop different diseases due to different character traits or
feelings (e.g., broken heart:heart attack, chip on the shoulder: arthritis in
the shoulder, etc), so maybe my stubborness contributes to my rigidity. Just
a thought. My dad cut out a cartoon for me once with a father leaving his
daughter's room after putting her to bed, and as he's leaving you hear, "And I
will let the bed bugs bite!" So, they say PD is "relentlessly debilitating",
etc., etc., I say _____ (please fill-in as you wish) to that! In some ways
it's my "friend", in that it makes me slow down and take it easy and listen to
what my body needs, rather than constantly running around like a nut (which I
do alot). Supposedly alot of native cultures believe those who are ill to be
blessed by the gods, because (although it may be against their will), they
gain a different perspective on life than those who are not so "blessed". So,
I guess we're all blessed, like it or not! It's kinda funny too that in my
'net surfing' I'm reading alot about a liver/platelet genetic type of defect
(see above articles for example), and my acupuncturist has all along been
treating my "blood" and kidneys/liver. Anyway, please excuse my digression.
I'm a bit punchy at the moment and tired (I recently moved and I find it more
stressful than previously due to the PD. My roomate's unpacked and ready to
go, and I'm still plodding along, but getting there). Although I love this
list for all the commentaries and information; like going to one of my support
meetings, it's sometimes depressing to think that my life will be reduced to
discussions about drug dosages and whether they cause constipation (at the
end of one of my first support group meetings that was the hot topic, and the
friend who accompanied me for the drive lightened things up by joking about
it). I have a friend who's wife is manic depressive and won't admit she's
ill. My roomate and I were talking about him and his wife, and about PD and
depression, the other night. I guess I'm just trying to fire myself up, and
whomever else cares, to fight the PD with everything without denying its
existence and effects. I must say that between this list and the other info
I've found on the web, I'm really excited about going to my next support group
meeting. Thanks to everyone, and especially to those organizing this list
and the new WWW homepage (and to those that actually read this entire
babble!). Wendy Tebay
