Biology 202
2004 First Web Paper
On Serendip

The disease first described as the "shaking palsy" and now known as Parkinson's disease was first discovered in 1817 by James Parkinson, for whom it was named. Parkinson's disease is a central nervous system disorder that affects approximately 1.5 million people in the United States alone. This disease results in a progressive and chronic loss of motor coordination, tremors, bradykinesia as well as other severe impairments (1). Research has shown that men are slightly more prone to the disorder than women, though the exact reason for this fact has yet to be discovered. In addition, the onset of this disorder is usually seen in people around 60 years of age. The disorder has also been known to affect younger people, however the rates of Parkinson's disease are extremely low in people under 40 years of age (1).

James Parkinson provided us with the challenge to resolve the connection between Parkinson's disease and the nervous system. As a result of his work, we now ponder as to why it is that a person suffering from Parkinson's disease cannot control their movement, despite the fact that they are trying to do so? It would be interesting to explore how this disease then affects the I-function.

Soon after James Parkinson described this "shaking palsy" disease it became a goal to research the cause of this disease. Through the examination of Parkinson's postmortem bodies, it was hypothesized that the substantia nigra was involved in this loss of motor control and coordination (2). They arrived at this conclusion by observing considerable amounts of apoptosis in the midbrain, specifically in the substantia nigra. With time there was an increase in knowledge about neurotransmitters and their role in neurotransmission in the nervous system. This knowledge identified that dopamine in the striatum of Parkinson's postmortem bodies was 80% lower than in healthy individuals (2). The fact that Parkinson's patients experience low levels of dopamine and apoptosis in the substantia nigra led many scientists to hypothesize that the substantia nigra generates dopamine, further implying that the low levels of dopamine paired with apoptosis led to the symptoms of Parkinson's disease.

In short, Parkinson's disease is caused by the degeneration of neurons in the substantia nigra which results in the decrease of dopamine. In addition, Mono Amine Oxidase-B breaks down the excess dopamine in the synapse further diminishing the dopamine that is left in the substantia nigra (3). Dopamine is vital for normal movements because it allows messages to be transmitted from the substantia nigra to the striatum, which then initiates and controls the ease of movement and balance (3). Furthermore, the loss of dopamine causes the neurons in the basal ganglia to fire randomly accounting for involuntary movements.

Acetylcholine is another neurotransmitter that is needed to produce smooth movements. In normal individuals there is a balance between acetylcholine and dopamine. In Parkinson's patients there is not sufficient dopamine to maintain the balance with acetylcholine (3). This irregular disproportion results in a lack of movement coordination leading to the more overt symptoms of Parkinson's.

It seems as if our brain is controlling the movement of our bodies without the individual having control over the disease. It would be great if there was an explanation as to the reduction of dopamine in the substantia niagra, but unfortunately there is not a concrete answer. There a many theories which seek to explain the cause of Parkison's. For example, some state that the disease is genetic ( "Parkin" gene) and others believe it is due to environmental toxins such as MPTP (4). MPTP causes Parkinson's like symptoms in drug abusers as seen through PET scans. Other studies conducted in rural areas have shown a higher frequency of Parkinson's in locations where herbicides and pesticides are prominent (5). Additional suggestions as to why dopamine degenerates are mitochondrial dysfunction and excitotoxicity (4). Extensive research is being conducted all over the world in an attempt to discover the definitive cause of Parkinson's disease. This is significant because once we identify what causes Parkinson's disease we can hope to prevent future occurrences of this disease as well as ultimately find a cure.

As mentioned earlier, there is no cure for Parkinson's disease. Therefore, the immediate goal of scientists is to find a drug that mimics dopamine, since dopamine itself is not allowed through the blood brain barrier. Researchers have thus far been successful in depicting the biological pathway of dopamine in the effort to replace the degenerating dopamine in the substantia nigra. This pathway shows that dopamine is derived from the amino acid tyrosine, which is converted into L-Dopa with the aid of the enzyme tyrosine hydroxilase. L-Dopa is then converted to dopamine by the enzyme L aromatic amino acid decarboxylase (L-AACD).

This biological pathway allowed scientist to discover that L-Dopa is able to cross the blood brain barrier giving scientist hope that L-Dopa might be converted to dopamine once it arrived to the brain. L-Dopa was found to be effective in reducing the harsh Parkinson's symptoms, meaning that L-Dopa actually converts to dopamine in the brain. L-Dopa is effective in the brain because the nervous system becomes up-regulated, and therefore craves the drug. In other words, the individual becomes highly sensitive to the drug. Unfortunately, L-Dopa also had severe side effects such as the inducement of vomiting and causing nausea. Later it was found that these side effects where caused due to the overexposure of L-AADC in the gastrointestinal tract. This was corrected by creating an L-AADC inhibitor which was unable to pass through the blood brain barrier. The L-AADC inhibitor allowed dopamine to successfully increase in the brain. There are many drugs for Parkinson's disease, but L-Dopa seems to be the most effective.

The issue of administering drugs in order to decrease the symptoms of Parkinson's disease is relatively controversial, since such administration can create tolerance to such drugs. As a patient's tolerance increases, the less effective the drug becomes and higher doses of the drug are required to discontinue the symptoms of Parkinson's. This leads to a dilemma; when does a doctor prescribe L-Dopa given that, due to the patient's progressively increasing tolerance to the drug, it cannot work forever? Does a doctor administer the drug during Parkinson's early stages when symptoms are becoming apparent or should they wait until Parkinson's is at its peak? It would be a tremendous success if there was a drug that would delay Parkinson's disease, but when the symptoms became severe, administer L-Dopa to regenerate dopamine in the substantia nigra.

Surgeries and implantations of embryonic cells have also been suggested to control the symptoms of Parkinson's disease, but none have been proven to be effective thus far (6).This gives us hope that we are working at making this disease as controllable as we can.

In essence, Parkinson's disease is a horrible disorder that kills many people all over the world. Unfortunately there is no cure for this disease, but many efforts are being made to control the prevalence of Parkinson's. In a positive note, thanks to Parkinson's disease we have learned a lot about the human body and its intricacies. It interesting to understand that malfunctions at a neuronal level can affect a person's life completely, in this case impairing people from controlling their movement. This research topic has allowed me to value how complex we are as humans and how fortunate I am to be healthy. Furthermore, while researching on Parkinson's disease I started thinking about the brain and behavior dichotomy. In this case it seems as though brain malfunctions are controlling behavior. So does brain actually equal behavior?

References:
1)National Institutes of Health , General Information on Parkinson's

2)Home Page, General Information on Parkinson's

3)Home Page, Brain and Parkinson's

4)Home Page, Causes of Parkinson's

5)Home Page, General Information

6)Home Page, Treatment of Parkinson's

7)Home Page, General Information

8)Home Page, Parkinson's and Pesticides


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