Parkinson's Disease Facts
Parkinson's disease (PD) is an age-related progressive deterioration of certain nerve systems in the brain, which affects movement, balance, and muscle control.
- Parkinson's disease is one of the most common movement disorders, affecting about 1% of people older than 60 years. Parkinson's disease is about 1.5 times more common in men than in women, and it becomes more likely to occur in people as they age. Parkinson's disease is not a hereditary disease.
- The average age of onset is about 60 years. Onset before age 40 years is relatively uncommon, but the much-publicized diagnosis of actor Michael J. Fox shows that younger people are also vulnerable.
- In Parkinson's disease, brain cells deteriorate (or degenerate) in an area of the brain called the substantia nigra. From the substantia nigra, specific nerve cell tracts connect to another part of the brain called the corpus striatum, where the neurotransmitter (a chemical messenger in the brain) called dopamine is released. Dopamine is an important neurotransmitter and alterations in its concentration can lead to the different medical problems seen in Parkinson's disease.
- The loss of these specific brain cells and decline in dopamine concentration are key steps that lead to the signs and symptoms of Parkinson's disease as well as are the target for treatments of Parkinson's disease. However, the biological, chemical, and genetic mechanisms responsible for the brain cell loss have not been identified with certainty.
Parkinson's Disease Causes
The causes of Parkinson disease remain unclear; clinicians and researchers have clear evidence that the nerve cells that produce dopamine in the brain's region known as the substantia nigra are altered and lost (destroyed). The challenge that remains is to discover how these neurons are destroyed to cause Parkinson's disease. Advances in genetics have lead researchers to discover that about 10% of people that develop the disease are due to multiple genetic factors, but these people usually are younger than 50. The majority of researchers suggest that a combination of genetic and environmental factors cause about 90% of cases of Parkinson's disease, but how these factors interact to alter and destroy brain cells thus producing Parkinson's disease is not well understood. A few theories and risk factors are listed below that may offer additional information and clues that may help lead to a better understanding of Parkinson's disease causes.
- Environment: Studies have found that living in a rural area, drinking well water, or being exposed to pesticides, herbicides, or wood pulp mills may increase a person's risk for developing Parkinson's disease.
- Oxidation hypothesis: Free radicals, generated from dopamine's oxidation, generate cell damage and death.
- It is thought that free radicals may play a role in the development of Parkinson's disease. Free radicals are atoms or groups of atoms with unpaired electrons that can damage cells and intracellular structures. Free radicals can be created when dopamine is broken down by combining it with oxygen.
- This breakdown of dopamine by an enzyme called monoamine oxidase (MAO) leads to the formation of hydrogen peroxide.
- A protein called glutathione normally breaks down the hydrogen peroxide quickly. If the hydrogen peroxide is not broken down correctly, it may lead to the formation of these free radicals, enhanced by the presence of iron, that then can react with cell membranes to cause lipid peroxidation (when the hydrogen peroxide interacts with lipids [fat-soluble substances] in the cell membrane). This leads to cell damage and cell death.
- The association of Parkinson's disease with increased dopamine turnover, decreased mechanisms (glutathione) to protect against free radical formation, increased iron (which makes it easier to create free radicals), and increased lipid peroxidation helps support the oxidation hypothesis.
- If this hypothesis turns out to be correct, it still does not explain why or how a loss of the protective mechanism occurs. An answer to this question may not be required. If the theory is correct, drugs may be developed to stop or delay these events.
- Alpha-synuclein alteration: The protein alpha-synuclein is involved in neurotransmitter release. This protein is a major component of Lewy bodies, which are found in the neurons of Parkinson's disease patients. The theory is that under certain conditions (genetic, environmental, or a combination of both) may lead to protein aggregates that develop in the Lewy bodies. During their development, some of the alpha-synuclein intermediates may be toxic to neurons. Other variations of this hypothesis suggest that lysosomes in the cells allow alpha-synuclein proteins to accumulate and then aggregate while other investigators suggest that Lewy bodies may develop like prions and may represent an autoimmune-like disease.
- Mitochondrial dysfunction: Mitochondrial activity in the cells of Parkinson's disease patients is reduced, so some investigators suggest that that whatever reduces this activity plays a causal role in Parkinson's disease. They conclude this because certain chemicals that can produce Parkinson's disease symptoms in humans cause disruption of mitochondrial functions and are effectively treated by dopamine.
- Some people have symptoms of Parkinson's disease that may have an identifiable cause. In this case, the syndrome is known as Parkinsonism or secondary Parkinson's disease. Parkinson's that is caused by drugs is probably far more common than reported and accounts for about 4% of all cases of Parkinson's. These findings give additional insight toward definition of potential Parkinson's disease causes.
- A change in the level of dopamine, whether by brain cell loss or drug use, can create the symptoms of Parkinson's disease.
- Interestingly, people who experience drug-induced Parkinson's may actually have a higher risk of developing Parkinson's disease later in life.
- A number of medications can cause Parkinson's by lowering dopamine levels. These are referred to as dopamine-receptor antagonists or blockers.
- Nearly all antipsychotic or neuroleptic medications such as chlorpromazine (Thorazine), haloperidol (Haldol), and thioridazine (Mellaril) can induce the symptoms of Parkinson's.
- The medication valproic acid (Depakote), a widely used antiseizure medication, may also cause a reversible form of Parkinson's.
- Medications such as metoclopramide (Octamide, Maxolon, Reglan), which is used to treat certain stomach disorders such as peptic ulcer disease, are capable of causing Parkinson's or making it worse.
- Antidepressants known as selective serotonin-reuptake inhibitors may cause symptoms similar to Parkinson's.
- These medications can alter the concentration of dopamine in the central nervous system.
Medically Reviewed by a Doctor on 9/16/2016
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