Parkinsons Disease Biology

7 Oct No Comments

Janet Lopez, Lisa Smith, Troye Wilson, Jaimee Howes

Excelsior College

Abstract

An article written by Tsuboi claims that the onset of Parkinson’s disease has a strong correlation with the combination of environment and genetic components. Several studies have indicated that there is a genetic factor contributing to the onset of the Parkinson’s disease. Some of these genes that are known to be the susceptibility genes are glucocerebrosidase, leucine-rich repeat kinase 2, and α-synuclein. Some research suggests that there are positive and negative effects from the environmental factors. An example that was provided was that smokers have more protection against the Parkinson disease, but there isa risk when it comes to pesticides that can cause the onset of the disease (Tsuboi, 2012). In this paper we will further synthesize the article by Tsuboi.

Keywords: pathogenesis, Parkinson’s disease, environment, genetic.

Does the environment and genetic factors really play a stronger role a role in the onset of the Parkinson’s disease versus genetics alone?According to the article titled, “Environmental-Genetic Interactions in the Pathogenesis of Parkinson’s Disease,” research indicates that there are many factors that influence Parkinson’s disease (PD) pathogenesis. These factors are genetic, aging and environmental. Findings suggest that there are correlations between the environmental and genetic factors. However, the genetic and environmental factors only pertain to the people who have developed the Parkinson’s disease prior to the age of fifty. This was concluded after a study was done on twins that showed no genetic factor who had developed PD after the age of fifty. It is important to note that these particular findings are based on a small sample and further research is required to confirm these findings. However, we will further analyze the statement the author has made and synthesize the article (Tsuboi, 2012).

Scientists did several studies on families that have PD in order to understand its complication and possible causes in the disease progression. (Tsuboi, 2012). The first family that was investigated lived in Italy, Contursi kindred. This family had an autosomal-dominant form of Parkinson’s disease. In this family, the symptom of PD did not show up until the individual was 46. The time PD presents itself, the individual has only 9 years before he dies. However, if levodopa treatment is given, symptoms of the continuous shaking of hands, can be kept minimal. Also, while the individual is taking the levodopa treatment, their cognitive and psychiatric features are also kept at a minimum. Another disorder of Parkinson’s disease called, sporadic PD, has similar symptoms except for the onset from when it develops. In 1997, scientists discovered that individuals with this contained a point mutation in the gene, a-synuclein. This was the first discovery of a point mutation in a single gene. (Tsuboi, 2012).

A second family that lived in Iowa was studied. They were shown to have Parkinson’s disease from a mutation in the SNCA gene that was different when compared to the Contursi family. Scientists found triplication in the area that contained the SNCA gene that resulted in the s-synuclein protein. The a-synuclein protein, however, was found to be doubled when compared to normal individuals. The onset of this PD is 35 and death usually occurs 8 years later. PD is extremely aggressive, but treatment with levodopa is helpful. However, sadly enough some individuals became cognitively impaired, had autonomic failure, and developed myoclonus. When a neuropathological analysis was done on both families, scientists found Lewy bodies which resulted in the families being compared to sporadic PD. Scientists believe that the presence of the SNCA gene is responsible for developing PD. (Tsuboi, 2012).

Environmental factors have been found to develop PD. The first chemical was found in 1983 and is called, MPTP (1-methyl-4-phenyl-1,2,2,6-tetrahydropyridine). MPTP was found to be a by-product of artificial opioid manufacturing. (Tsuboi, 2012). On the other hand, some environmental agents are known to protect or be against PD. The risk factors include herbicides, pesticides, and even metals. Some environmental factors that are known to protect against PD are smoking, drinking coffee, and even sodas that contain caffeine. In smoking individuals, the homozygous CC genotype located at GSTP1-114 is found to be protective. Caffeine provides protection against PD by blocking the adenosine receptor A2A (ADORA2A). Even though caffeine is consumed by CYP1A2 enzyme, it aids in providing neuroprotection. (Tsuboi, 2012).

Scientists have also found that environmental-genetic interactions can aid in the development of PD. For example, scientists found that an enzyme, cytochrome P450(CYP) 2D6, is responsible for metabolizing xenobiotics that are contained in the liver. They also found that organophosphate pesticides, the herbicide atrazine, and MPTP are responsible for the development of PD. Another example of environmental genetic influence found is the gene, SLC6A3. This gene is responsible for transporting dopamine to the brain for functioning. It is the polymorphism of SLC6A3 that is a risk of developing PD. When a group of alleles from the SLC6A3 gene combine with pesticide exposure, this also has been shown to increase the chance of developing PD. This was proven when the California Central Valley did a study on risk alleles when exposed to paraquat and maneb. Scientists even found that monoamine increases the risk for PD. However, in the study of MAO’s, it is the gene MAO-B polymorphisms that increases the risk for PD. The interaction of glutathione S- transferase (GST) can be closely related to the antioxidant and detoxifying properties of xenobiotic substrates. The genotype paraoxonase 1 (PON1), has also been proven to increase the risk of PD when exposed to organophosphate. This also includes exposure to the insecticide diazinon. (Tsuboi, 2012).

The author made two statements within his article pertaining to genetic factors to make his point of view clear. The first assumption the author made is that the SNCA genes contributes to sporadic PD. The second assumption is that another gene (leucine-rich repeat kinase 2) also plays a role in both sporadic and familial PD. The author failed to inform the reader what the total number of cases are in Caucasians from North Africa, he only provided the percentage and this can be out of only 3 people. We are not sure; it lacks value to the statement. The Asian population lacks the LRRK2- G2019S mutation. Only a few (5 families) PD patients actually have SNCA. There needs to be a larger study on families who have PD. PD is very complex and there are many forms of PD. Long term studies seem to be helpful, but research should be focus on genes and see if there is a common genetic factor on a larger group. There may be a genetic component, but it may differ based on race. Therefore, studies on different race (Asian, Caucasian) should be done for comparison. The data collected lacks the connection of the genetic factors, it only provided a small percentage and it was not concise. This data was not enough to justify the author’s claims. There are no clear connections genetically between the different types of PD and there only real connection that seems to be a bit clear is the suggestion that the sporadic characteristics are similar throughout other types of PD.  There was only one statement that did support notion that there is a genetic correlation to PD, but not the question in study. This was the percentage provided by the author, that there was 40% of North African Caucasian PD cases (sporadic and familial) found to have the LRRK2-G2019S mutation. This only tells us that there actually may be a genetic factor in North African PD with the genetic mutation specifically with the LRRK2-G2019S gene.  The statement made by the author is suggesting that there is a correlation between environmental and genetic factors that contribute to PD. Both together work hand-in-hand according to the author. However, the information provided lacks evidence that there actually is a genetic factor correlation of PD (Tsuboi, 2012).

References

Tsuboi, Y. (2012, April 22). Environmental-Genetic Interactions in the Pathogenesis of Parkinson’s Disease. Retrieved November 08, 2016, from https://mycourses.excelsior.edu/courses/1/BLA.BIO320.Online.201610.201612.s30043581/messaging/users/_291716_1/attachments/269a70b6c3984413b7b3dd9d0af93489/en-21-123.pdf




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