Parkinson’s disease causes in detail

From what I can gather from research papers, the disease may have multiple causes, some environmental, some genetic, some illness related and so on.  In other words, trying to trace back the cause and effect chain to some ultimate cause is fruitless because there may be numerous ultimate causes.  There is however some very compelling evidence that links environmental causes  - particularly free radicals - with parkinson’s disease….

Gene mutation

At least 5% of people are now known to have forms of the disease that occur because of a mutation of one of several specific genes. Here the evidence is quite strong, but it is not known what definitively causes the mutations.  The following paper, however, suggests that the cause may be ‘free radical mediated’.

The most common radical in the lower atmosphere is molecular dioxygen.  Molecular oxygen is relatively unreactive at room temperature except in the presence of a catalytic heavy atom such as iron or copper, so these may have a part to play, as we shall see.

Other environmental free radicals occur in smog.  Persistent radicals are generated in great quantity during combustion.  So there is a high concentration in any city or industrial estate where motor vehicles and heating systems as well as any incineration plants or industrial plants operate.  When a hydrocarbon is burned, a large number of different oxygen radicals are involved.

Excessive amounts of these free radicals can lead to [cell injury] and death.  Many forms of cancer, for example, are thought to be the result of reactions between free radicals and DNA, resulting in mutations that can adversely affect the cell cycle and potentially lead to malignancy.  In addition free radicals contribute to alcohol-induced liver damage, perhaps more than alcohol itself.  And as we have seen above, free radicals may also be involved in Parkinson's disease.

Generally our body has some defences against free radicals but vitamin deficiencies can lead to damage.  Three vitamins, vitamin A, vitamin C and vitamin E and polyphenol antioxidants are key antioxidants. Further, there is good evidence uric acid can act as an antioxidant to help neutralize certain free radicals.

Inherited Genetic

There are some people that appear to inherit a defective gene or genes. Around 15% of individuals with PD have a near relative who has the disease.  However, this does not actually prove the link, it only shows they might have been subjected to the same environmental factors that cause a mutation on the gene.

Mutations in specific genes have been conclusively shown to cause PD. These genes code for alpha-synuclein (SNCA), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), parkin (PRKN), leucine-rich repeat kinase 2 (LRRK2 or dardarin), PTEN-induced putative kinase 1 (PINK1), DJ-1 and ATP13A2.   In most cases, people with these mutations will develop PD.

Dietary

We have already seen that vitamin deficiency may be a cause of Parkinson’s if the person is exposed to free radicals, as the person has lost their defences.  We also saw that uric acid can act as an antioxidant to help neutralize certain free radicals.  If uric acid levels are low, again the body’s defences have been reduced against free radical damage.

Uric acid is created when the body breaks down purine nucleotides.

Purines are found in high concentration in meat and meat products, especially internal organs such as liver and kidney. Examples of high-purine meat and fish sources include: sweetbreads, anchovies, sardines, liver, beef kidneys, brains, meat extracts (e.g., Oxo, Bovril), herring, mackerel, scallops, game meats, beer (from the yeast) and gravy. 

Examples of foods which have a moderate amount of purine  are beef, pork, poultry, and other fish and seafood not mentioned above.

A diet poor in these foodstuffs will thus contribute to the damage done by free radicals as the body will not have the defences it needs to counteract the attack.

Plant based diets are generally low in purines.  So already we have an indication that a person on a vegetarian diet is at increased risk.  In terms of vegetables,  asparagus, cauliflower, spinach, mushrooms, green peas, lentils, dried peas, beans, oatmeal, wheat bran, wheat germ, and hawthorn contain moderate to low amounts.

Low dietary zinc intake can cause lower uric acid levels.

Other notable purines are hypoxanthine, xanthine, theobromine and caffeine.  Caffeine is of course found in coffee, but also in guarana, yerbamate, tea and kola.  Theobromine is found in chocolate and yerba mate.  If you don’t eat chocolate and only drink caffeine free drinks, you may be at risk if you live in an environment in which you are subjected to high free radicals.

Heavy metals

We saw that the most common radical in the lower atmosphere is molecular dioxygen [O2] and that molecular oxygen is relatively unreactive at room temperature except in the presence of a catalytic heavy atom such as iron or copper.  Some research seems to indicate that these heavy metals play a part by reacting with this common radical, and from there the path is that we saw in the last sub-section – cell death.  In effect, high levels of certain heavy metals particularly in the blood react with the oxygen in the blood to create free radicals.

It is worth adding that the presence of heavy metals in the blood can be even more pronounced in women taking oral contraceptive medication or HRT.  Estrogen increases the half life of Cu, so women with very high estrogen levels and intense blood loss during menstruation are likely to have a high Cu/Fe.  There is the possibility that they are at particularly increased risk during the menopause when estrogen levels are fluctuating wildly and blood loss can be extraordinarily high.

But where do these heavy metals come from?

One source is incinerators.  Although theoretically the European community, for example, regulates the emissions of waste incinerators which are found ironically in hospitals as well as towns and cities as municipal waste disposal mechanisms, there is still concern about the regulation and it is known that arsenic, cadmium, cobalt, chromium, copper, mercury, manganese, nickel, lead, tin, and thallium, are all emitted during  incineration. Waste-derived fuels are especially prone to contain heavy metals, so heavy metals are a concern in consideration of waste as fuel.

Heavy metal pollution can also arise from the purification of metals, e.g., the smelting of copper and the preparation of nuclear fuels. Any plant which processes iron to produce steel will probably result in heavy metal pollutants entering the atmosphere.  Electroplating is the primary source of chromium and cadmium.

We do not have to breathe them to necessarily suffer from them.  Through precipitation of their compounds or by ion exchange into soils and muds, heavy metal pollutants can lay dormant. Unlike organic pollutants, heavy metals do not decay.  Any plants grown in the area polluted may take up the pollutants.  If these are plants used in food products, the cycle will eventually lead back to us.

There are plants and microrganisms that are particularly effective at taking up heavy metal.  These are sometimes used to remove some heavy metals such as mercury. Plants which exhibit ‘hyper accumulation’ can be used to remove heavy metals from soils by concentrating them in their bio matter. But outside of this controlled use at a more general level, these same plants may then be eaten by cattle for example or sheep which then come back to us as food.

One of the largest problems associated with the persistence of heavy metals is the potential for bioaccumulation and biomagnification causing heavier exposure for some organisms than is present in the environment alone. Coastal fish and seabirds (such as the Atlantic Puffin) are often monitored for the presence of such contaminants being particularly susceptible. If we eat fish from a polluted area, we may be ingesting heavy metals.

Inflammation and the immune system

The following describes a long chain of cause and effects. 

Dopamine quinone is the oxidised derivative of dopamine.  It is harmful, acting as a free radical. 

Dopamine can be converted into dopamine quinone in the presence of COX-2.

Cyclooxygenase-2 (COX-2, prostaglandin H synthase-2, PGHS-2) is unexpressed under normal conditions in most cells, but elevated levels are found during inflammation which is why the use of Ibuprofen helps to inhibit it.

Inflammation is usually a by-product  of the immune system and there is considerable evidence that indeed the immune system influences the brain.  Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis and psychiatric disorders all have links to inflammation and particularly neuroinflammation.

So if there is injury and the cells are causing inflammation or if the person has an auto immune disease, there is a risk of developing Parkinson’s disease.  Bacterially caused inflammation may have the same effect.

Lipopolysaccharides (LPS), also known as lipoglycans, are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.

The following evidence is interesting because it shows the additional links with the heavy metals.

Toxins such as pesticides

There are studies that link toxins such as pesticides with PD, particularly pesticides on food, as people’s exposure to pesticides under normal conditions is actually quite low…..

Paraquat, for example,  is the trade name for N,N?-dimethyl-4,4?-bipyridinium dichloride, one of the most widely used herbicides in the world. Paraquat, a viologen, is quick-acting and non-selective, killing green plant tissue on contact. It is also toxic to human beings and animals. Research has shown that it is linked to development of Parkinson's disease.

Bilirubin is responsible for the yellow color of bruises, the yellow color of urine (via its reduced breakdown product, urobilin), the brown color of faeces (via its conversion to stercobilin), and the yellow discoloration in jaundice.  It is excreted in bile and urine, and elevated levels may indicate certain diseases or the presence of toxins in the blood.

Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells.  Heme oxygenase-1 (HO-1) is an enzyme that converts heme to free iron, carbon monoxide (CO) and biliverdin (bilirubin precursor) and  is only produced in response to various stressors.  Thus elevated biliverdin levels indicate elevated HO-1 levels and elevated HO-1 levels indicate a stressor of some sort.

And  HO-1 is up-regulated in PD- and Alzheimer's disease-affected neural tissues indicating a toxic basis for some instances of the disease.

Overall

I think we can see that most of the causes of Parkinson’s disease are environmental and the causes are self-inflicted causes, in that man has caused them to man.

It is us that burn hydrocarbons, use incinerators, have factories that produce plastics and metals, drive cars and lorries, use pesticides and other toxins and eat ‘junk’ foods.

The toxins or bacterial agents or viruses or similar act on certain genes and cause them to mutate, thus meaning certain cells in the brain malfunction or die.  Some of the cells which are killed are dopamine producing cells which is why dopamine is often reduced in parkinson’s disease sufferers, but this is not the cause of PD, it just happens to be one of many effects.  The absence of dopamine will in turn have its effects, so the symptoms [as we shall see] end up being quite complex – a combination of those resulting from brain neuron death and those related to reduction in this neurotransmitter.