Parkinson's Disease - What Causes the Disease?
Parkinson's disease occurs when certain nerve cells, or neurons, in an area of the brain known as the substantia nigra die or become impaired. Normally, these neurons produce an important brain chemical known as dopamine. Dopamine is a chemical messenger responsible for transmitting signals between the substantia nigra and the next "relay station" of the brain, the corpus striatum, to produce smooth, purposeful muscle activity. Loss of dopamine causes the nerve cells of the striatum to fire out of control, leaving patients unable to direct or control their movements in a normal manner. Studies have shown that Parkinson's patients have a loss of 80 percent or more of dopamine-producing cells in the substantia nigra. The cause of this cell death or impairment is not known but significant findings by research scientists continue to yield fascinating new clues to the disease.
One theory holds that free radicals -- unstable and potentially damaging molecules generated by normal chemical reactions in the body -- may contribute to nerve cell death thereby leading to Parkinson's disease. Free radicals are unstable because they lack one electron; in an attempt to replace this missing electron, free radicals react with neighboring molecules (especially metals such as iron), in a process called oxidation. Oxidation is thought to cause damage to tissues, including neurons. Normally, free radical damage is kept under control by antioxidants, chemicals that protect cells from this damage. Evidence that oxidative mechanisms may cause or contribute to Parkinson's disease includes the finding that patients with the disease have increased brain levels of iron, especially in the substantia nigra, and decreased levels of ferritin, which serves as a protective mechanism by chelating or forming a ring around the iron, and isolating it.
Some scientists have suggested that Parkinson's disease may occur when either an external or an internal toxin selectively destroys dopaminergic neurons. An environmental risk factor such as exposure to pesticides or a toxin in the food supply is an example of the kind of external trigger that could hypothetically cause Parkinson's disease. The theory is based on the fact that there are a number of toxins, such as 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) and neuroleptic drugs, known to induce parkinsonian symptoms in humans. So far, however, no research has provided conclusive proof that a toxin is the cause of the disease.
A relatively new theory explores the role of genetic factors in the development of Parkinson's disease. Fifteen to twenty percent of Parkinson's patients have a close relative who has experienced parkinsonian symptoms (such as a tremor). After studies in animals showed that MPTP interferes with the function of mitochondria within nerve cells, investigators became interested in the possibility that impairment in mitochondrial DNA may be the cause of Parkinson's disease. Mitochondria are essential organelles found in all animal cells that convert the energy in food into fuel for the cells.
Yet another theory proposes that Parkinson's disease occurs when, for unknown reasons, the normal, age-related wearing away of dopamine-producing neurons accelerates in certain individuals. This theory is supported by the knowledge that loss of antioxidative protective mechanisms is associated with both Parkinson's disease and increasing age.
Many researchers believe that a combination of these four mechanisms -- oxidative damage, environmental toxins, genetic predisposition, and accelerated aging -- may ultimately be shown to cause the disease.p>Return To Table of ContentsSOURCES:>NIH ">Return To Table of Contents