CAUSES OF PARKINSON'S DISEASE

CAUSES OF IDIOPATHIC PARKINSON'S DISEASE

There are a variety of causes of Parkinson's Disease including toxic, 
genetic, head trauma, drug induced, plus a number of medical disorders that 
can cause the same symptoms. However, these causes of Parkinson's Disease 
represent only a minority of cases. The majority of people with Parkinson's 
Disease suffer from idiopathic Parkinson's Disease, which is effectively no 
obvious initiating cause. The question as to what causes idiopathic 
Parkinson's Disease becomes simpler if it is divided between what initiates 
it, and what eventually causes it to be maintained.

Initial causes
The primary symptoms of Parkinson's disease are due to excessive muscle 
contraction. Acetylcholine stimulates muscle contraction. Dopamine reduces 
muscle contraction. So Parkinson's Disease consequently occurs when the 
effect of dopamine is less than that of acetylcholine. Dopamine deficiency 
rather than acetylcholine excess is normally responsible for this occurring. 
However, before somebody is prone to developing Parkinson's Disease they 
must be producing sufficient acetylcholine. That is why somebody could lack 
dopamine yet still not get Parkinson's Disease.

The dopaminergic neurons are the cells that produce dopamine. Although it is 
widely claimed that there is overwhelming loss of these cells, no such study 
actually proves this. What such studies prove is that there is eventually a 
massive loss of cell activity in Parkinson's Disease rather than a massive 
loss of cells.

Enzymes are also needed to produce dopamine. Enzymes are substances that 
enable a chemical reaction to take place in the body. There are only two 
that are (almost) unique to Parkinson's Disease. However, unless there is a 
genetic disorder, which is rare, enzymes will be produced at the onset of 
Parkinson's Disease. The level of functioning of enzymes is regulated almost 
entirely by how well dopamine is being produced.

Dopamine is produced via the following mechanism - L-tyrosine >>> L-dopa >>> 
Dopamine. L-tyrosine is essential for this function. Udenfriend's study 
(Journal of biological chemistry [1964] 239 : 2910) showed how the levels of 
L-dopa go up an down in response to the level of L-tyrosine. Other studies 
have shown how dopamine levels rise or fall in people with Parkinson's 
Disease in response to L-tyrosine levels. Tyrosine will not just appear. 
Somebody would have to consume it (or L-phenylalanine which is a substance 
that can make it). L-tyrosine is prone to deficiency, and so has the 
potential to be one of the factors that contributes to the onset of 
Parkinson's Disease. For more information go to Biochemistry of Parkinson's 
Disease.

The formation of dopamine also requires three coenzymes : THFA, pyridoxal 
phosphate, NADH. Coenzymes will only be produced if the vitamin required to 
make them is in sufficient quantities. The vitamins required for the 
formation of these three coenzymes are folic acid (for THFA), pyridoxine 
(vitamin B6) (for pyridoxal phosphate), and nicotinamide (vitamin B3) (for 
NADH). It is very easy to become deficient in any of these substances as 
they are not widely available in large quantities.

The formation of dopamine also requires two cofactors. Those shown to be 
essential for the formation of dopamine are ferrous iron and zinc. Enzyme 
studies have shown how the levels of the relevant enzymes required to form 
dopamine rise or fall in response to the concentration of these substances. 
Manganese is additionally needed for the action of dopamine. So these three 
substances are inevitably potential factors in the initial onset of 
Parkinson's Disease.

In summary, a lack of those substances needed for the production and action 
of dopamine (L-tyrosine, ferrous iron, zinc, pyridoxine, nicotinamide, folic 
acid, manganese) would lead to low levels of dopamine and the cell damage 
that is characteristic of Parkinson's Disease. It is not necessarily a 
deficiency of any one of these substances. There could literally be any 
combination or permutation of deficiency of any of these substances that 
could lead to a dopamine deficiency. The initial onset of Parkinson's 
Disease is consistent with there being a combination deficiency of those 
substances known to be essential for the formation of dopamine. There is not 
a single piece of scientific, biochemical or clinical evidence that opposes 
this.

Eventual causes
Those substances needed to form dopamine will normally decline in their 
quantities even further over time. Although the intakes of these substances 
will fluctuate from day to day, a deficiency of them can take many months 
and more to reverse. The deficiency of some substances such as iron can take 
a considerable amount of time to reverse. Once established the deficiencies 
tend not to be reversed unless there is a concerted effort.

Cell damage occurs as a result of Parkinson's Disease, because when dopamine 
is not properly formed, the toxic element Superoxide ion is formed instead. 
Cell damage itself could help to contribute to further deterioration. 
However what is being considered is what causes Parkinson's Disease, not 
what perpetuates it. It is a reduction in dopamine that initially leads to 
cell damage rather than the cell damage that initially reduces dopamine 
formation. Certain elements within the cells can reproduce, so much of the 
damage is reversible.

Parkinson's disease drugs can certainly relieve many people's symptoms in 
the relative short term and longer. However, the after effect of any 
stimulatory drug ends up causing an opposite after effect. So drugs for 
Parkinson's Disease can be both a cure and eventual cause of symptoms. This 
does not mean that somebody should never have taken Parkinson's Disease 
drugs. Somebody should not also instantly cease their Parkinson's Disease 
drugs. They would get almost immediate withdrawal symptoms. It is just an 
unfortunate fact for drugs of many disorders that there is not only side 
effects, but an eventual opposite after effect that contributes to the 
medical disorder it initially relieved.

TOXIC CAUSES
There are a number of toxins that may cause Parkinson's disease or cause 
symptoms mimicking Parkinson's disease. These include : Paraquat 
(herbicide), Rotenone (pesticide), Maneb (fungicide), Manganese, MPTP (drug 
by product), Toluene (solvent), N-hexane (solvent), Carbon disulfide 
(usually in solvents or pesticides), Carbon monoxide, Mercury, Cyanide, and 
Copper. For more information go to Toxic causes of Parkinson's Disease.

GENETIC CAUSES
There are also genetic causes of Parkinson's Disease, that can be inherited 
or acquired. These include genetic mutations named PARK1, PARK2, PARK3, 
PARK5, PARK6, PARK7, PARK8, and PARK12. Rather than inevitably cause 
Parkinson's Disease, these genetic mutations normally make somebody more 
prone to developing Parkinson's Disease. For more information go to Genetic 
causes of Parkinson's Disease.

HEAD TRAUMA
A prior head injury with amnesia or loss of consciousness was associated 
with an increased risk of developing Parkinson's Disease. The risk was 
increased further after subsequent head injuries and with head injuries 
requiring hospitalisation. People who experienced a mild head trauma with 
only amnesia had no increased risk of developing Parkinson's Disease. Recall 
bias might have an effect on the outcome of these studies, because many 
people with Parkinson's Disease reflect on the cause of their illness, and 
so may remember head trauma more readily than those that do not have it.

DRUG INDUCED
Some of the Anti-psychotics - drugs that are used to treat schizophrenia and 
psychosis - can induce the symptoms of Parkinson's disease by lowering 
dopaminergic activity, as can Trimetazidine. Due to feedback inhibition, 
L-dopa can eventually cause the symptoms of Parkinson's Disease that it 
initially relieves. Dopamine receptors can also eventually contribute to 
Parkinson's disease symptoms by decreasing the sensitivity of dopamine 
receptors.

INNOCENT CAUSES OF SYMPTOMS
Symptoms of Parkinson's Disease can be caused by more innocent means that 
are not actually Parkinson's Disease. For these reasons, for every person 
that is diagnosed with Parkinson's Disease, there are probably ten to a 
hundred people that do not have Parkinson's Disease, but that get symptoms 
no different from those of Parkinson's Disease.

Muscular injury can cause symptoms identical to those of Parkinson's Disease 
including rigidity, loss or lessening of physical movement and even tremor. 
The difference between this and Parkinson's Disease is that symptoms only 
appear in the injured muscles, rather than there being an effect on muscles 
generally. Also, the symptoms, instead of tending to get worse, will usually 
decline within hours or days or weeks of the injury.

Muscular strain can cause symptoms identical to those of Parkinson's Disease 
including rigidity, loss or lessening of physical movement and even tremor. 
Walking or running long distances can cause muscle rigidity for days 
afterwards. Lengthy use of the muscles of the hand, can cause stiffness or 
even tremor in the muscles most used. Consequently many of the instances of 
symptoms of Parkinson's Disease may consequently be due to muscular strain. 
The difference between this and Parkinson's Disease is that symptoms only 
appear in the strained muscles, rather than there being an effect on muscles 
generally. Also, the symptoms, instead of tending to get worse, will usually 
decline within minutes or hours or days of ceasing the use of those muscles.

Cold temperature can cause symptoms identical to those of Parkinson's 
Disease including rigidity, loss or lessening of physical movement and 
tremor, either by being in a cold place, in cold water or by consuming cold 
drinks. Shivering is simply a cold temperature tremor. That is very probably 
why people with Parkinson's Disease can tend towards increased symptoms 
during colder weather. The effect of the cold temperature is adding to the 
symptoms that they already have.

Stress can cause the symptoms of Parkinson's Disease in somebody that 
doesn't have it, and exacerbate the symptoms in somebody that does. This is 
because stress causes the formation of adrenaline, which increases 
acteylcholine, which increases muscle contraction - the primary symptom in 
Parkinson's Disease. This is why even people that don't have Parkinson's 
Disease can get stiffened muscles when they are stressed, and even shake 
with fear, as if they had tremor. What the body does in response to this is 
produce dopamine, because dopamine reduces excessive muscle contraction. 
Somebody with Parkinson's Disease can not produce sufficient dopamine, which 
is why the muscles contract excessively in Parkinson's Disease regardless of 
whether or not somebody is stressed. So stress is not a "cause" of 
Parkinson's Disease in that on its own it can not perpetuate the symptoms 
long term.

 ©2006-2009 Viartis
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Rayilyn Brown
Director AZNPF
Arizona Chapter National Parkinson Foundation
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