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Parkinson disease (PD) is a progressive movement disorder marked by tremors, rigidity, slow movements (bradykinesia), and posture instability. It occurs when cells in one of the movement-control centers of the brain begin to die for unknown reasons. PD was first noted by British physician James Parkinson in the early 1800s.
Usually beginning in a person's late fifties or early sixties, Parkinson disease causes a progressive decline in movement control, affecting the ability to control initiation, speed, and smoothness of motion. Symptoms of PD are seen in up to 15% of those ages 65–74, and almost 30% of those ages 75–84.
Most cases of PD are sporadic. This means that there is a spontaneous and permanent change in nucleotide sequences (the building blocks of genes). Sporadic mutations also involve unknown environmental factors in combination with genetic abnormalities. The abnormal gene (mutated gene) will form an altered end-product or protein. This will cause abnormalities in specific areas in the body where the protein is used. Some evidence suggests that the disease is transmitted by autosomal dominant inheritance. This implies that an affected parent has a 50% chance of transmitting the disease to any child. This type of inheritance is not commonly observed. The most recent evidence is linking PD with a gene that codes for a protein called alpha-synuclein. Further research is attempting to fully understand the relationship with this protein and nerve cell degeneration.
PD affects approximately 500,000 people in the United States, both men and women, with as many as 50,000 new cases each year.
The immediate cause of PD is degeneration of brain cells in the area known as the substantia nigra, one of the movement control centers of the brain. Damage to this area leads to the cluster of symptoms known as "parkinsonism." In PD, degenerating brain cells contain Lewy bodies, which help identify the disease. The cell death leading to parkinsonism may be caused by a number of conditions, including infection, trauma, and poisoning. Some drugs given for psychosis, such as haloperidol (Haldol) or chlorpromazine (thorazine), may cause parkinsonism. When no cause for nigral cell degeneration can be found, the disorder is called idiopathic parkinsonism, or Parkinson disease. Parkinsonism may be seen in
The substantia nigra, or "black substance," is one of the principal movement control centers in the brain. By releasing the neurotransmitter known as dopamine, it helps to refine movement patterns throughout the body. The dopamine released by nerve cells of substantia nigra stimulates another brain region, the corpus striatum. Without enough dopamine, the corpus striatum cannot control its targets, and so on down the line. Ultimately, the movement patterns of walking, writing, reaching for objects, and other basic actions cannot function properly, resulting in the symptoms of parkinsonism.
There are some known toxins that can cause parkinsonism, most notoriously a chemical called MPTP, found as an impurity in some illegal drugs. Parkinsonian symptoms appear within hours of ingestion, and are permanent. MPTP may exert its effects through generation of toxic molecular fragments called free radicals, and reducing free radicals has been a target of several experimental treatments for PD using antioxidants.
It is possible that early exposure to some as-yetunidentified environmental toxin or virus leads to undetected nigral cell death, and PD then manifests as normal age-related decline brings the number of functioning nigral cells below the threshold needed for normal movement. It is also possible that, for genetic reasons, some people are simply born with fewer cells in their substantia nigra than others, and they develop PD as a consequence of normal decline.
Author Info: Laith Farid Gulli MD, The Gale Group Inc., Gale, Detroit, Gale Encyclopedia of Genetic Disorders Part I, 2002
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