Parkinson's disease results from the as-yet unexplained death of dopamine-producing neurons whose cell bodies live in the upper brainstem region called the substantia nigra. To date there are many factors implicated at initiating this process ranging from genetic aberrations and environmental toxins to stress and even minor head trauma. Somehow these factors lead to the abnormal accumulation of the evil protein, alpha-synuclein thought to disrupt cell function to the point of cell death.
Investigators may have discovered that missing link between exposure and lethal protein accumulation. Scientists at St. Louis University have identified a natural toxic substance produced in the brain called "dopal" that may be the missing link or at least part of the as yet undiscovered process that occurs between exposure to known initiating factors like pesticides, herbicides, manganese and the lethal accumulation of monkey-wrench protein, alpha-synuclein.
According to lead scientist W. Michael Panneton, Ph.D., professor of pharmacological and physiological science at Saint Louis University School of Medicine, "In Parkinson disease, we knew that the death of dopamine cells is responsible for patients' symptoms. But no one knew why the cells are dying."
Dopal, the newly discovered toxic substance seems to cause clumping of alpha-synuclein protein. At the very least, knowing this fact opens up a new window for treatments to prevent disease progression. By the time the classic movement symptoms develop in Parkinson's disease (tremor, rigidity and slowness) as many as 80 percent of dopamine neurons from the tiny brain region from where they originate (substantia nigra) have already died. Any treatment geared towards prevention of further death of that small remaining reserve of dopamine-producing cells would be a boon to the treatment of the disease which now mainly consists of using drugs that either mimic the deficient dopamine, or increase its presence in the brain by various mechanisms.
Dopal is the natural by-product of dopamine breakdown, particularly when acted on by the enzyme class called the monoamine oxidases. The anti-Parkinson's drug rasagiline blocks this breakdown (called a monoamine oxidase inhibitor or MAOI), to increase the amount of brain dopamine. At least a few studies have suggested it as being effective at slowing the disease progression. If you block these monoamine oxidase enzymes in the brain you may be lowering the amount of dopal being produced so this may be the mechanism for how rasagiline slows Parkinson's disease progression, i.e., by leaving less dopal around, and thus resulting in less lethal clumping of alpha-synuclein protein.
It has also been suggested by other researchers that somehow, the classic environmental toxins thought to induce Parkinson's like pesticides may somehow stimulate the metabolism of dopamine to dopal.
Obviously more research is needed but this does solve at least one important piece in the puzzle as to why dopamine-cells die in Parkinson's disease.
Marshall Davidson, M.D.,aka. "Dopadoc," a physician who battles early-onset (age 44, 2005) Parkinson's disease. He maintains the website "Dopadoc's Parkinson's Journal" at http://www.dopadoc.com/
To quote, "I am a doctor with Parkinson's Disease. I firmly believe that the better a basic knowledge you have of your disease, the more you'll be able to make competent care decisions for yourself and weed out bad doctors and outright quacks. My website aims to provide the lay person with essential information crucial to taking charge of your care. Take a look for yourself and raise your medical IQ. We even have a basic Parkinson's curriculum you can enroll in for free."
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