Hi olsen!!
The basal ganglia is the region in the brain that controls the body
movements and coordinates changes in posture.
It comprises the following areas of the brain: the striatum, the
globus pallidus, the substantia nigra, and the subthalamic nucleus.
The proper function of the neurons of the basal ganglia require a
balance of two neurotransmitters (the chemical messengers that enable
the forwarding -or transmission- of electrical impulses along and
between nerve pathways) dopamine and acetylcholine. Dopamine is
responsible for transmitting signals between the substantia nigra and
the striatum:
"The nigrostriatal pathway is a neural pathway which connects the
substantia nigra with the striatum. It is one of the major dopamine
pathways in the brain, and is particularly involved in the production
of movement, as part of a system called the basal ganglia motor loop."
"Nigrostriatal pathway" - Wikipedia, the free encyclopedia
http://en.wikipedia.org/wiki/Nigrostriatal_pathway
In Parkinson's disease the nerve cells in the substantia nigra (where
the dopamine is made) die, and surviving cells do not produce enough
dopamine. This disturbs the balance between dopamine and
acetylcholine and causes the nerve cells of the striatum to fire out
of control, producing the inability to control movements in a normal
way. The symptoms of the disease typically do not show themselves
until the lost of about 80% of dopamine producing cells at the
substantia nigra.
All the above info is well known, but the problem is to find what is
the exact cause of the death of the cells at the substantia nigra.
One newly theory holds that free radicals and/or peroxides damage
molecules generated by normal chemical reactions in the brain and
contribute to nerve cell death, leading to Parkinson's disease.
The excess of free radicals and peroxides in the body and the
subsequent effects is called Oxidative Stress.
See "What is Oxidative Stress?"
http://www.genox.com/what.htm
At normal levels of free radicals and peroxides the damage caused by
oxidative stress is kept under control by antioxidant chemicals.
It is well known that patients with Parkinson's disease have increased
levels of iron in the brain, especially in the substantia nigra, and
decreased levels of ferritin, which is a protein in the body that
binds to iron forming a ring around the iron isolating it.
The excess of free iron (Fe2+) start the formation of free radicals
from its interaction with hydrogen peroxide and leading to promotion
of membrane lipid peroxides and consequent cell death:
"Oxygen-derived free radicals have recently been implicated in
pathogenesis of various diseases including atherosclerosis, diabetes
mellitus, epilepsy, inflammatory diseases and cancer. Lipid
peroxidation induced by free radicals is believed to be one of the
major causes of cell membrane damage leading to lysis of cell.
The body possesses a complex protective antioxidant system against
these potentially toxic products such as vitamin E, vitamin C, vitamin
A, glutathione and antioxidant enzymes. These enzymes include
glutathione reductase (GR), glutathione peroxidase (GP), superoxide
dismutase (SOD) and catalase (CT).
In Parkinson's disease (PD), there is progressive death of substantia
nigral cells leading to less availability of dopamine to the striatum
which controls movement. Neurons of substantia nigra (SN) may be
particularly vulnerable to oxidant stress, because the oxidative
metabolism of dopamine has the potential to generate cytotoxic free
radicals. Dopamine can be oxidized by either monoamine oxidase or
undergo autooxidation to generate hydrogen peroxide (H2O2). H2O2 can
damage the neuron directly or indirectly through the formation of
hydroxyl radicals in presence of ferrous ions. Neuromelanin present
within the SN neurons has the potential to promote site-specific
accumulation and reduction of iron thereby potentiating iron-induced
lipid peroxidation and consequent cell death. H2O2 is normally
detoxified by reduced glutathione (GSH) in the reaction catalyzed by
GP, thus an increased rate of dopamine turnover or a deficiency of GSH
could lead to oxidative stress. Thus, it appears that free radicals
may be one of the important agents responsible for destruction of SN
neurons, thereby leading to PD."
From "Free radical toxicity and antioxidants in Parkinson?s disease"
by Sudha K, Rao A, Rao S, Rao A - Neurol India 2003;51:60-62:
http://www.neurologyindia.com/article.asp?issn=0028-3886;year=2003;volume=51;issue=1;spage=60;epage=62;aulast=Sudha
This lead to the conclusion that a misbalance between free radicals
and antioxidants at the substantia nigra derives in an oxidative
stress that may cause or contribute to Parkinson's disease.
This is in simple words the theory of how the oxidative system in the body
leads to parkinson symptoms.
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For additional reference and further explanations I will post links to
several articles related to this:
"Causes of Parkinson's Disease":
http://www.holistic-online.com/Remedies/Parkinson/pd_causes.htm
"OXIDATIVE STRESS IN PARKINSON'S DISEASE":
http://sulcus.berkeley.edu/mcb/165_001/papers/manuscripts/_412.html
"Parkinson's Disease and Glutathione (GSH)"
http://www.1whey2health.com/parkinsons_glutathione.htm
"Oxidative stress in neurodegeneration: cause or consequence?" by
Julie K Andersen. Nature Reviews Neuroscience 5, S18?S25 (2004):
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v10/n7s/full/nrn1434.html
"Parkinson's Disease as Multifactorial Oxidative Neurodegeneration:
Implications for Integrative Management" by Parris M. Kidd, PhD
http://www.thorne.com/pdf/journal/5-6/parkinsons_disease.pdf
"Glutathione, oxidative stress and neurodegeneration" by Jörg B.
Schulz, Jörg Lindenau, Jan Seyfried and Johannes Dichgans:
http://www.blackwell-synergy.com/links/doi/10.1046/j.1432-1327.2000.01595.x/full/
"Chemistry and Biochemistry of Oxidative Stress in Neurodegenerative
Disease" by Sayre L.M.; Smith M.A.; Perry G. - Current Medicinal
Chemistry June 2001, vol. 8, no. 7, pp. 721-738(18):
To view this article you must register to this site, it is free.
http://www.ingenta.com/isis/searching/Expand/ingenta?pub=infobike://ben/cmc/2001/00000008/00000007/art00002
"Glutathione in Parkinson's Disease - Scientific Research Abstracts"
http://www.1whey2health.com/glutathione_parkinsons.htm
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Search strategy:
oxidative parkinson
"oxidative stress"
"oxidative stress" parkinson
I hope that this helps. Remember to not consider this answer ended
until your entire satisfaction. So please feel free to use the
clarification feature to request further assistance on this topic
before rate this answer.
Best regards.
livioflores-ga |
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