TOXIC CAUSES OF IDIOPATHIC PARKINSON'S DISEASE

PARAQUAT

Paraquat is a quaternary ammonium herbicide. Other members of this class include

 diquat, cyperquat, diethamqua, difenzoquat and morfamquat. Pesticides are known

 to be associated with an increased rate of Parkinson’s Disease.

 Paraquat structurally resembles MPTP and its metabolite MPP+. MPTP and

 MPP+ are neurotoxic chemicals, that induce Parkinson’s Disease in exposed humans.

Paraquat might therefore might, as do MPTP and MPP+ inhibit tyrosine hydroxylation,

which is essential for the formation of dopamine.

ROTENONE Rotenone is an insecticide that has the potential to cause Parkinson's disease. Insecticides are also known to affect well water. Rotenone is commonly used in powdered  form to treat parasitic mites on chickens and other fowl, and of certain tropical legumes. Rotenone inhibits of dopamine. So rotenone could cause   Parkinson's disease by lowering dopamine levels. When given intravenously to mice, rotenone has been demonstrated to cause a model of Parkinson's disease. Rotenone toxicity is tyrosine hydroxylation, which is essential for the formation also caused by complex I inhibition, depletion of cellular and oxidative damage. These processes cause loss of midbrain  dopaminergic neurons, leading to depletion of dopamine in the brain. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ MANEB Maneb is a fungicide that contains manganese. The major active element of Maneb is manganese ethylene-bis-dithiocarbamate. Pesticides are known to be associated with an increased rate of Parkinson's disease, so there is a greatly increased the  likelihood of developing toxic symptoms by people involved in horticulture and agriculture. As Maneb contains manganese it is possible that it causes Parkinson's Disease symptoms via the same means as manganese, which is by inhibiting tyrosine hydroxylation, which is essential for the formation of dopamine. The effects of Maneb are potentiated when there is also exposure to the pesticide Paraquat. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ MANGANESE Manganese can cause manganism, an irreversible neurological disorder similar to Parkinson's disease. Occupational exposures occur mainly in welding, mining as miners are surrounded by manganese dust and airborne manganese particles, alloy production, processing, ferro-manganese operations  especially in which manganese ore or manganese compounds are turned into steel, and work with agrochemicals. The towns and communities surrounding the areas of manganese heavy industry could also become affected by toxic exposure to manganese. It is also hypothesized that long-term exposure to the naturally-occurring manganese in shower water also puts people at risk. Manganese inhibits tyrosine hydroxylation, which is essential for the formation of dopamine. So manganese may cause Parkinson's disease by lowering dopamine levels. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ MPTP MPTP (1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine) is a chemical that may be  produced accidentally during illicit manufacture of the recreational drug MPPP,  which is a synthetic heroin substitute. The neurotoxicity of MPTP wasdiscovered in 1976  after a chemistry graduate student synthesized MPPP incorrectly and injected the result.  It was contaminated with MPTP, and within three days he began exhibiting symptoms  of acute Parkinson's disease. It was also developed but unused as a herbicide and  was distributed on the streets as a synthetic opioid-like drug.  MPTP inhibits tyrosine hydroxylation, which is essential for the formation of dopamine.  So MPTP causes acute Parkinson's disease by lowering dopamine levels. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ TOLUENE Toluene is a solvent that has been shown to cause Parkinson's Disease, or that has been  associated with people with Parkinson's disease. Toluene is used as an octane booster  in fuel, as a solvent in paints, paint thinners, chemical reactions, rubber, printing,  adhesives, lacquers, leather tanning, disinfectants, and to produce phenol and TNT (a component of explosives). It is also used as a raw material for toluene  di-isocyanate, which is used in the manufacture of polyurethane foams.  The precise means of toxicity of toluene is not known. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ N-HEXANE N-hexane, a constituent of solvents has been shown to cause parkinsonism. Most of the  n-hexane used in industry is mixed with similar chemicals called solvents. The major  use for solvents containing n-hexane is to extract vegetable oils from crops such as soybeans.  These solvents are also used as cleaning agents in the printing, textile, furniture, and shoe   making industries, and also by chemists. Certain glues used in the roofing, and shoe  and leather industries also contain n-hexane. Several consumer products contain n-hexane,  such as gasoline, spot removers, quick-drying glues, and also rubber cement.  The means of  toxicity of n-hexane is still unknown. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ CARBON DISULFIDE Carbon disulfide, usually in solvents or pesticides, can cause Parkinson's disease that is  associated with other neurological symptoms. The toxic effects can persist for years  after exposure to the carbon disulfide has ceased. Potential sources include pesticides  used as fumigants, disulfiram (a drug used in the treatment of chronic alcoholism), i ndustrial solvents, solvents used in the production of viscose rayon and cellophane film.  Means of toxicity is not established. However, carbon disulphide interferes with  pyridoxal 5-phosphate. Pyridoxal 5-phosphate is essential for the formation of  dopamine from L-dopa. So carbon disulphide may cause Parkinson's disease symptoms  by reducing the formation of L-dopa. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ CARBON MONOXIDE Carbon monoxide toxicity is frequent due to the formation of carbon monoxide  by very common means such as gas cookers and exhaust fumes. However, it normally  requires severe exposure (e.g. the person going into a coma as a result of the  carbon monoxide poisoning) before symptoms of Parkinson's disease develop.  Carbon monoxide causes hemoglobin (which transports oxygen) to turn in to  carboxyhemoglobin (which does not transport oxygen). Oxygen is required  for the formation of L-dopa. So carbon monoxide may cause Parkinson's  disease symptoms by interfering with the availability of oxygen to the brain.  However, the means by which it can cause parkinsonism has still not been proven. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ MERCURY Mercury toxicity is a known cause of symptoms that mimic Parkinson's disease, especially  tremor. One of the chief targets of the toxin is the enzyme pyruvate dehydrogenase (PDH).  The enzyme is irreversibly inhibited by severalmercury compounds, the lipoic acid  component of the multienzyme complex binds mercury compounds tightly and  thus inhibits PDH. However, the cause of the symptoms of Parkinson's disease  is likely to be due to the fact that mercury potently causes the release of dopamine,  thereby lowering dopamine levels. Mercury is found in a wide variety of sources:  dietary fish intake, ethnic over-the-counter medications, occupational exposures to mercury  vapour, possession of dental amalgam fillings, gold production, skin ointment, some soaps. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ CYANIDE Cyanide, usually from the consumption of potassium cyanide or sodium cyanide can  result in Parkinsonism. Cyanide is also produced by certain bacteria, fungi, and algae,  and are found in a number of foods and plants, such as unprocessed cassava, cherry pits,  apricot pits, bitter almonds. Hydrogen cyanide is contained in vehicle exhaust  and in tobacco smoke, as does burning plastic. Cyanides are also found in gold processing.  Cyanide interrupts the electron transport chain in the inner membrane of the   mitochondrion. Cyanide also occupies the place of oxygen in hemoglobin  (which transports oxygen). Oxygen is required for the formation of L-dopa. So carbon   monoxide may cause Parkinson's disease symptoms by interfering with the availability  of oxygen to the brain. However, the precise toxic means by which it causes  Parkinson's disease has still not been proven. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ COPPER Copper accumulates in Wilson's disease, which is associated with Parkinson's disease. Although copper may cause symptoms by other means, there do not appear to be published studies in which copper has otherwise caused Parkinson's disease. This may be because copper is not normally formed in to a vapour or dust that can readily be inhaled or consumed. Copper can be found in high quantities in copper mines, copper cooking pots, copper plumbing, very excessive consumption of copper nutritional supplements. Excess copper can cause the formation of a copper-dopamine complex,  which leads to the oxidation of dopamine to amino chrome. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ LEAD Prolonged exposure to lead can double the likelihood of developing Parkinson’s Disease. Common means of lead poisoning are lead contaminated soil, and ingestion of lead  dust or chips from deteriorating lead-based paints. Lead has also been found in drinking  water, from plumbing fixtures that are either made of lead or have trace amounts of  lead in them. Lead can be found incosmetics in some countries, and in toys such as  many from China. Due to the similarity of their structures, lead can inadvertently replace  iron in enzymatic reactions, but it does not properly function as a cofactor. This might  cause a reduction in L-dopa because iron is an essential cofactor for L-dopa formation.  Lead can also interfere with oxygen transport by reducing hemoglobin biosynthesis. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ TRICHLOROETHYLENE People subjected to chronic industrial exposure of the solvent Trichloroethylene have been  found to have Parkinson’s Disease. Trichloroethylene is a solvent, that is used  extensively in industry and the military and is a common environmental contaminant.  It has been used to extract vegetable oils, in coffee decaffeination, and in the preparation  of flavouring extracts from hops and spices. The precise means of toxicity is unknown. Workers with workstations adjacent to the source of trichloroethylene and who were subjected to chronic inhalation and dermal exposure from handling trichloroethylene-soaked metal parts all had Parkinson's disease. Lesser chronic  respiratory exposure to trichloroethylene led to many features of Parkinsonism,  including significant motor slowing. Under the trade name Tilene, trichloroethylene was used as an anesthetic and as an  inhaled obstetrical analgesic in millions of patients.  Tilene has been found to cause shaking and stiffness.