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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 [log in to unmask] Rayilyn Brown Director AZNPF Arizona Chapter National Parkinson Foundation [log in to unmask] ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn