is the role of Dopamine?
are Antioxidants important?
does Glutathione therapy help in Parkinson's Disease?
is Glutathione being used in Parkinson's disease treatments?
Abstracts on Glutathione and Parkinson's Disease
What is Parkinson's Disease?
Disease (PD) is named after Dr. James Parkinson, a London physician
who is credited with being the first to describe this disease in
to the National Parkinson Foundation (www.parkinson.org),
PD is a slowly progressing disease of the nervous system. Occurring
in one out of every 100 individuals over 65 years of age, PD results
in progressive neurodegeneration that ends in death, due primarily
to secondary complications such as infection.
involves a selective loss of neurons in an area of the midbrain
called the substantia nigra. One of the mechanisms contributing
to neuron loss in the substantia nigra is damage by reactive oxygen
species - a destructive class of molecules, including free
radicals - produced by oxidation of the neurotransmitter dopamine.
What is the role of Dopamine?
is called a neurotransmitter, as it is a chemical messenger between
brain or nerve cells. A gradual degeneration or reduction in nigral
cells results in the reduction of nigral dopamine.
cells of the substantia nigra use dopamine to communicate with the
cells in another region of the brain called the striatum. Thus,
the reduction in nigral dopamine also results in a decrease in striatal
symptoms - motor function deficiencies characterized by muscle rigidity,
jerky movements, rhythmic resting tremors and the inability to initiate
or complete voluntary movement - are the result of inadequate striatal
striatal dopamine is believed to cause the PD symptoms, most drugs
used to treat PD are aimed at temporarily replenishing or mimicking
dopamine. Such drugs are called dopaminergic drugs. They
improve some symptoms, but do not restore normal brain function
nor halt brain cell deterioration.
drugs can overstimulate nerve cells elsewhere in the body and cause
confusion, hallucinations, nausea and fluctuations in the movement
of limbs. Dopaminergic drugs are generally effective at first in
reducing many PD symptoms, but lose their effect over time and cause
severe side effects.
loss of dopaminergic neurons in Parkinson's disease results in enhanced
metabolism of dopamine, augmenting the formation of H2O2, thus leading
to generation of highly neurotoxic hydroxyl radicals (OH').
generation of free radicals can also be produced by 6-hydroxydopamine
(6-OHDA) or 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)
which destroys striatal dopaminergic neurons causing Parkinsonism.
most important free radical scavenger in the cells of the substantia
nigra is the powerful brain antioxidant, glutathione. Glutathione
levels in PD patients are low.
have shown that age-related loss of glutathione in the dopaminergic
neurons of the substantia nigra can bring about various changes
in the cells.
changes, in combination with dopamine oxidation, appear to hasten
cell death and advance the progression of PD.
least 80% of the Substantia Nigra cells must be lost before symptoms
of Parkinson's disease are observed. Therefore protection or maintenance
of these cells under oxidant stress is essential.
injuries, illnesses such as encephalitis, medicines, illicit drugs
and possibly other chemicals that increase free radical production,
have been shown to cause nigral damage and result in Parkinson-like
Jimmy Gutman: "The brain is particularly
susceptible to free radical attack because it generates more oxidative-by-products
per gram of tissue than any other organ. The brain's main antioxidant
is glutathione - it's importance cannot be overstated.
stress and glutathione are important factors in such various disorders
as brain injury, neurodegenerative disease, schizophrenia, Down
syndrome and other pathologies.
neurological and psychiatric disease processes are characterized
by high levels of oxidative stress and free radical formation, as
well as abnormalities in glutathione metabolism and antioxidant
radicals and oxyradicals have been recognized by psychoneurobiologist
as playing an important role in the development and progression
of many of these disorders."
How does Glutathione help in Parkinson's Disease?
are several factors that explain why glutathione is so beneficial
in Parkinsonís disease. First, glutathione has the unique ability
to make certain areas of the brain more sensitive to dopamine, so
that even though dopamine is decreased, it nevertheless becomes
In addition glutathione
has profound antioxidant activity - protecting the
brain from free radical damage. But an even more intriguing benefit
of glutathione lies in its powerful detoxification ability.
has long been recognized that most Parkinsonís patientís manifest
flaws in their ability to detoxify various chemicals to which they
not every person exposed to pesticides or other toxins develops
Parkinsonís disease, those unfortunate few who harbor an inherited
flaw in their detoxification pathways are at far greater risk to
the brain damaging effects of a wide variety of toxins.
is one of the most important components of the liverís detoxification
system. Glutathione therapy is one of the most effective techniques
for enhancing liver and brain detoxification.
treatments considerably improve some of the symptoms of Parkinson's
disease including difficulties with rigidity, walking, movement,
coordination and speech. A marked reduction of tremor has been observed
as well as a decrease in depression.
(both antioxidants) were very effective in protecting the nerves
in the substantia nigra from being destroyed by oxidative stress."
- Ray Strand, M.D.
How is Glutathione being used in Parkinson's
practical problem in increasing glutathione levels is that taking
glutathione itself as a supplement does not boost cellular glutathione
levels, since glutathione breaks down in the digestive tract before
it reaches the cells. However, intravenous glutathione therapy and
precursors are both effective in boosting intracellular levels
glutathione injections are described in Life Extension magazine's
February 2001 issue as having amazing results, amazingly quickly:
"Within less than an hour of the injection, Parkinson's patients
experienced an almost complete restoration of the ability to
walk, turn around and move their arms."
even a single dosage of intravenous glutathione, many of the symptoms
of Parkinsonís disease are rapidly improved, often, in as little
as 15 minutes.
David Perlmutter, a pioneer in this therapy, has developed a
protocol utilized at the Perlmutter Health Center for administering
intravenous glutathione to Parkinson's patients.
Perlmutter: "Eighty to ninety percent improve dramatically.
It's felt that the mechanism that allows it to work is in increasing
the sensitivity to certain receptors to dopamine.
doesn't raise dopamine levels, but it allows the dopamine in
the brain to be more effective. Glutathione not only
increases sensitivity to dopamine, but also to serotonin, which
may explain why many of our depressed PD patients have a remarkable
information on Dr. Perlmutter
glutathione is available from:
Wellness Health and Pharmaceuticals
2800 South 18th Street
Birmingham, Alabama 35209
Telephone: (800) 227-2627
Fax: (800) 369-0302
antioxidants and supplements that increase cellular glutathione,
such as alpha lipoic acid, NAC, pycnogenol, the herb silymarin
(milk thistle), and un-denatured, whey protein
are effective in restoring normal function.
(NAC) enhances the bodyís production of glutathione and aids
the detoxification process. Other nutritional supplements which
aid the detoxification process include selenium, vitamins E
and C. Undenatured
whey protein is also a good source of glutathione precursors.
Research Abstracts on Glutathione and Parkinson's Disease
oxidative stress and neurodegeneration.
Schulz JB, Lindenau J, Seyfried J, Dichgans [J.Eur J Biochem
Parkinson's disease, progressive supranuclear palsy and glutathione
metabolism in the substantia nigra of patients.
Perry TL, Yong VW. [Neurosci Lett 1986 Jun 30;67(3):269-74]
in glutathione levels in Parkinson's disease and other neurodegenerative
disorders affecting basal ganglia
Sian J, Dexter DT, Lees AJ, Daniel S, Agid Y, Javoy-Agid F,
Jenner P, Marsden CD [Ann Neurol, 36(3):348-55 1994 Sep]
stress as a cause of nigral cell death in Parkinson's disease
and incidental Lewy body disease
P, Dexter DT, Sian J, Schapira AH, Marsden CD [Ann Neurol
impairment as an early event in the process of apoptosis induced
by glutathione depletion in neuronal cells: relevance to Parkinson's
Merad-Boudia M, Nicole A, Santiard-Baron D, Saille C, Ceballos-Picot
I. [Biochem Pharmacol 1998 Sep 1;56(5):645-55]
oxidative stress participate in nerve cell death in Parkinson's
Hirsch EC. [Eur Neurol 1993;33 Suppl 1:52-9]
mitochondrial function, iron metabolism and glutathione levels
in Parkinson's disease
P. [Acta Neurol Scand Suppl 1993;146:6-13]
of brain glutathione potentiates the effect of 6-hydroxydopamine
in a rat model of Parkinson's disease
JC, Remires D, Leiva A, Gonzalez R.[ J Mol Neurosci 2000
glutathione results in calcium-mediated cell death in PC12
Jurma OP, Hom DG, Andersen JK. [Free Radic Biol Med
depletion switches nitric oxide neurotrophic effects to cell
death in midbrain cultures: implications for Parkinson's disease
Canals S, Casarejos MJ, de Bernardo S, Rodriguez-Martin E, Mena
MA. [J Neurochem. 2001 Dec;79(6):1183-95.]
depletion in PC12 results in selective inhibition of mitochondrial
complex I activity. Implications for Parkinson's disease
Jha N, Jurma O, Lalli G, Liu Y, Pettus EH, Greenamyre JT, Liu
RM, Forman HJ, Andersen JK. [J Biol Chem. 2000 Aug 25;275(34):26096-101.]
study of markers of oxidative stress and metabolism of blood
iron in Parkinson's disease] [Article in Spanish]
Larumbe Ilundain R, Ferrer Valls JV, Vines Rueda JJ, Guerrero
D, Fraile P. [Rev Esp Salud Publica 2001 Jan-Feb;75(1):43-53]
open trial of high-dosage antioxidants in early Parkinson's
Stanley Fahn. American Journal of Clinical Nutrition 53
Prevention of dipamine-induced cell death by thiol antioxidants:
Possible implication for treatment of Parkinson's disease
D. Offen, et al. Experimental Neurology 141, no. 1 (September
Oxidative stress and antioxidant therapy in Parkinson's disease
M. Ebadi, et al. Progress in Neurobiology 48, no. 1 (January
Effects of tocopherol and deprenyl on the progression of disability
in early Parkinson's disease
The Parkinson Study Group. New England Journal of Medicine
328, no. 3 (January 21, 1993): 176-183.
scientific research abstracts on Glutathione and Parkinson's
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