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Glutathione (GSH) in the etiology and treatment of Parkinson's Disease

Copyright © 2002 1Whey2Health
Reproduction Prohibited

What is Parkinson's Disease?

What is the role of Dopamine?

Why are Antioxidants important?

How does Glutathione therapy help in Parkinson's Disease?

How is Glutathione being used in Parkinson's disease treatments?

Research Abstracts on Glutathione and Parkinson's Disease



What is Parkinson's Disease?

Parkinson's Disease (PD) is named after Dr. James Parkinson, a London physician who is credited with being the first to describe this disease in 1817.

According 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.

PD 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?

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.

The 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 dopamine.

PD 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 dopamine.

Since 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.

Dopaminergic 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.



Why are Antioxidants important?

The 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').

The 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.

The 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.

Studies have shown that age-related loss of glutathione in the dopaminergic neurons of the substantia nigra can bring about various changes in the cells.

These changes, in combination with dopamine oxidation, appear to hasten cell death and advance the progression of PD.

At 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.

Certain 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 symptoms.

Dr. 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.

Oxidative stress and glutathione are important factors in such various disorders as brain injury, neurodegenerative disease, schizophrenia, Down syndrome and other pathologies.

Many 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 defenses.

Free 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?

There 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 more effective.

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.

It has long been recognized that most Parkinsonís patientís manifest flaws in their ability to detoxify various chemicals to which they are exposed.

While 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.

Glutathione 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.

Glutathione 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.

"Glutathione and N-acetyl-L-cysteine (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 disease treatments?

The 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 taking glutathione precursors are both effective in boosting intracellular levels of glutathione.

Intravenous Glutathione Therapy:

Intravenous 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."

Following even a single dosage of intravenous glutathione, many of the symptoms of Parkinsonís disease are rapidly improved, often, in as little as 15 minutes.

Dr. 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.

Dr. 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.

Glutathione 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 improvement."

More information on Dr. Perlmutter

Injectable glutathione is available from:
Wellness Health and Pharmaceuticals
2800 South 18th Street
Birmingham, Alabama 35209
Telephone: (800) 227-2627
Fax: (800) 369-0302

Glutathione Precursors:

Dietary 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.

N-acetyl-cysteine (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

Glutathione, oxidative stress and neurodegeneration.
Schulz JB, Lindenau J, Seyfried J, Dichgans
[J.Eur J Biochem 2000 Aug;267(16):4904-11]

Idiopathic 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]

Alterations 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]

Oxidative stress as a cause of nigral cell death in Parkinson's disease and incidental Lewy body disease
Jenner P, Dexter DT, Sian J, Schapira AH, Marsden CD [Ann Neurol 1992;32 Suppl:S82-7].

Mitochondrial impairment as an early event in the process of apoptosis induced by glutathione depletion in neuronal cells: relevance to Parkinson's disease.
Merad-Boudia M, Nicole A, Santiard-Baron D, Saille C, Ceballos-Picot I.
[Biochem Pharmacol 1998 Sep 1;56(5):645-55]

Does oxidative stress participate in nerve cell death in Parkinson's disease?
Hirsch EC.
[Eur Neurol 1993;33 Suppl 1:52-9]

Altered mitochondrial function, iron metabolism and glutathione levels in Parkinson's disease
Jenner P. [Acta Neurol Scand Suppl 1993;146:6-13]

Depletion of brain glutathione potentiates the effect of 6-hydroxydopamine in a rat model of Parkinson's disease
Garcia JC, Remires D, Leiva A, Gonzalez R.[ J Mol Neurosci 2000 Jun;14(3):147-53]

Decreased glutathione results in calcium-mediated cell death in PC12
Jurma OP, Hom DG, Andersen JK. [Free Radic Biol Med 1997;23(7):1055-66]

Glutathione 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.]

Glutathione 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.]

[Case-control 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]

An open trial of high-dosage antioxidants in early Parkinson's disease
Stanley Fahn
. American Journal of Clinical Nutrition 53 (1991): 380S-382S.

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 1996): 32-39.

Oxidative stress and antioxidant therapy in Parkinson's disease
M. Ebadi, et al.
Progress in Neurobiology 48, no. 1 (January 1996): 1-19.

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.

More scientific research abstracts on Glutathione and Parkinson's Disease


Parkinson's Disease Resources

"James", a site about Parkinson's Disease
This web site is about Parkinson's Disease; what it is, where you can get support, what you can do to fight its effects, and how the Internet can help. It is a project of the Adrienne Coles Memorial Trust.


 


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