Parkinson’s Disease

According to National Institute of Neurological Disorders and Stroke (n.d.), Parkinson's Disease is the second most common neurological disorder after Alzheimers. It is estimated to affect one million people in just the United States, and $14 billion is spent annually treating it. Also (Publishing, 2020), ten million people are estimated to suffer from Parkinson's Worldwide. Parkinson's is a chronic and progressive disease. This means that this disease persists and worsens over time.

Many aspects of Parkinson's Disease are still a mystery to scientists today. However, research is being conducted and we hope to find ways to help people in the diagnosis and treatment of Parkinson's.

What is Parkinson's?

According to Lewy Body Dementia (LBD) (2022), Parkinson's disease is a neurological condition in which patients experience uncontrolled movements such as shaking, stiffness, and difficulty balancing/coordinating. Patients also experience, according to Tolosa et al. (2021) memory loss, hyposmia (loss of smell), constipation, urinary dysfunction, orthostatic hypotension, depression, pain, and sleep disturbances. Typically, early signs of this illness arise in people over the age of sixty, but in some rarer cases people begin seeing symptoms in their fifties. Parkinson's is the second most common neurodegenerative disease with no cure. However, studies have suggested that getting regular aerobic exercise can reduce the chances of getting Parkinson's.

Chronic Care- Parkinson's Disease (Source)

Treatments/Medications

There are some treatments to relieve the symptoms of Parkinson's disease (Publishing, 2020). First, medication. Levodopa is a drug and amino acid that replenishes the brain's supply of dopamine, which is a neurotransmitter that Parkinson's patients do not have enough of. Dopamine assists with movement. With this drug, there are side effects which can be eased with more medication. Carbidopa is used in combination with Levodopa to help reduce nausea, low blood pressure, and restlessness that come with taking Levodopa. There are also Amantadine, which increases dopamine levels that are already in the brain and Anticholinergic medications, which reduce tremor. Catechol-O-methyltransferase inhibitors and Monoamine Oxidase B inhibitors both block enzymes that break down dopamine, allowing for the body to conserve as much dopamine as it can.

Parkinson's association: Parkinson's Patients Have Less Dopamine (Source)

According to Publishing (2020), besides medication, people with Parkinson's disease can go through different therapies. Two examples of therapies are Deep Brain Stimulation and Focused Ultrasound. Typically, Deep Brain Stimulation is for people who do not respond well to medication. In this procedure, thin metal wires are inserted into the brain, where they send electrical pulses to ease motor symptoms. However, this is not recommended for patients suffering from dementia as well. Focused Ultrasound for tremor is another FDA-approved option that destroys brain cells that cause motor problems. However, this option is permanent and irreversible, unlike Deep Brain Stimulation.

NCBI- Deep Brain Stimulation (Source)

Hereditary vs Sporadic

According to The Genetic Link to Parkinson's Disease (n.d.), Parkinson's disease can be hereditary or sporadic. Certain gene mutations can lead to the increased likelihood of development/development of the disease. However, scientists are still unsure what the exact cause is. This means you cannot always know if you are going to get Parkinson's disease. Sporadic Parkinson's disease is more common, affecting about 90% of all Parkinson's disease patients.

Causes for Parkinson's Disease

According to Lewy Body Dementia (LBD) (2022), Studies have shown that alpha-synuclein is a protein that is very important in the development of Parkinson's disease (PD). Scientists are still not fully sure what alpha-synuclein's purpose in the body is. It is important to note that there are many factors, internal and external, that can lead to PD. A-synuclein is just one of the major factors. This is mainly through the creation of Lewy Bodies. Lewy Bodies are clumps of abnormal particles of protein. They contain aggravated, or misfolded, clumps of a-synuclein. Accumulation/aggravation occurs when proteins (like alpha-synuclein) are too large to be degraded and/or the enzymes that break down proteins are lesser in number. The accumulation of Lewy bodies blocks dopamine production and transmission, leading to difficulty controlling movements. It also interferes with Acetylcholine, a neurotransmitter that is responsible for memory, thinking, and processing. This is what leads to the dementia aspect of PD. Lewy Bodies cause either some or all of the motor symptoms of Parkinson's, but scientists haven't been able to fully prove that they are the direct cause.

NCBI- Lewy Body (Source)

Genes that lead to Susceptibility to Hereditary Parkinson's Disease

According to The Genetic Link to Parkinson's Disease (n.d.), in Parkinson's disease, genes can be the reason patients are more susceptible to Parkinson's. Certain genes work differently than others. In hereditary Parkinson's disease, there are five main genes that cause a patient to be likely to get Parkinson's. Some genes cause Parkinson's in an autosomal dominant pattern. This is when only one copy of a mutated gene needs to be inside a person's body (inherited by a parent) in order to make the individual more susceptible to Parkinson's. Two examples of genes that can cause Parkinson's this way are.

1. (Mutated) LRRK2- This gene codes for a protein kinase, which is an enzyme that regulates proteins (such as alpha-synuclein).
2. (Mutated) SNCA- Codes Alpha-synuclein.

There are also genes that work in an autosomal recessive pattern, which means two copies of a mutated gene (inherited by one or both parents) need to exist for Parkinson's to be more likely to occur. These genes include:

1. (Mutated) PARK2: The PARK2 gene makes the protein parkin, which normally helps cells break down and recycle proteins.
2. (Mutated) PARK7: Mutations in this gene cause a rare form of early-onset Parkinson's disease. The PARK7 gene makes the protein DJ-1, which protects against mitochondrial stress.
3. (Mutated) PINK1: The protein made by PINK1 is a protein kinase that protects mitochondria (structures inside cells) from stress. PINK1 mutations occur in early-onset Parkinson's disease.

It's important to note that a very small percentage of the population have family history of Parkinson's disease. Most cases are sporadic.

Molecular events in neurons undergoing neurodegeneration in PD (Source)

Recent Research

According to Du et al. (2020), recent studies have shown that alpha-synuclein oligomers are a cause of Parkinson's disease. An oligomer is formed by the non-covalent binding (binding without electrons) of proteins to create a macromolecular complex (an assembly of large molecules). These oligomers are toxic to nerve cells in our brain. They can be toxic in many ways, causing mitochondrial dysfunction (leads to nerve damage and cell death), endoplasmic reticulum stress (leads to cell loss), loss of proteostasis (the regulation of proteins in the body), synaptic impairment (impairment of connections between neurons), cell apoptosis (cell self-destruction), and neuroinflammation (inflammation in the nervous system).

MDPI- Alpha Synuclein Oligomers into Aggregated Beta Sheets and Fibrils (Source)

Many of these symptoms caused by alpha-synuclein oligomers lead to neuron failure/dysfunction and therefore Parkinson's disease. However, this is an ongoing study, so we are not sure how the exact mechanisms work.

Future Directions

Currently, there are still many unanswered questions about Parkinson's disease. In fact, the actual cause of it is still speculation. There are many possible factors, such as Lewy bodies, alpha-synuclein oligomers, and genetic mutations/SNPs. But if scientists are able to pinpoint one certain cause, they would be able to create treatment much easier.

Also, currently there is no way to diagnose Parkinson's disease. Until there are symptoms and patients respond to medicine, we cannot be sure that an individual has Parkinson's disease. I think these are two huge unanswered questions that need to be solved in order for us to really understand the disease. We are also still unsure exactly what alpha-synuclein, a huge factor in Parkinson's disease, does. These seem like three major factors (probably not easy to figure out) that scientists should focus on in order to create proper, effective treatment.

Additionally, I believe that Lewy Body Dementia and Parkinson's disease (as well as Alzheimers) are very similar to each other in terms of causes and symptoms. I definitely think scientists need to look into comparing the two diseases and genetics of the two diseases if they haven't already.

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Impact Statement

Hello, I'm Annika Thakur. I am a sophomore in high school with a particular passion for biology. I've been interested in this field for around two years. This year I wrote a research paper and created a poster on Parkinson's Disease with Elio Academy. My report and poster were done on my own with guidance from my instructor. It was my favorite part of the two-week program I attended. My class was fully online, and a great experience where I got to learn through both lectures and hands-on activities. Through this program, I learned about creating academic works of writing, but also other biological topics such as protein structure, neurobiology, and immunology. Students were even able to request topics for the instructor to teach us. Overall, I had fun with my project and learned a lot with Elio Academy. I now hope to pursue biology even more in the future.

References

1. Du, X., Xie, X., & Liu, R. (2020). The Role of α-Synuclein Oligomers in Parkinson's Disease. International Journal of Molecular Sciences, 21(22), 8645. https://doi.org/10.3390/ijms21228645

2. Lewy Body Dementia (LBD). (2022). www.hopkinsmedicine.org . https://www.hopkinsmedicine.org/health/conditions-and-diseases/dementia/dementia-with-lewy-bodies

3. Parkinson's Disease: Causes, Symptoms, and Treatments. (2022, April 14). National Institute on Aging. [https://www.nia.nih.gov/health/parkinsons-disease#:~:](https://www.nia.nih.gov/health/parkinsons-disease](https://www.nia.nih.gov/health/parkinsons-disease#:~:text=While%20genetics%20is%20thought%20to)

4. Parkinson's Disease: Challenges, Progress, and Promise | National Institute of Neurological Disorders and Stroke. (n.d.). Www.ninds.nih.gov. https://www.ninds.nih.gov/current-research/focus-disorders/focus-parkinsons-disease-research/parkinsons-disease-challenges-progress-and-promise

5. Publishing, H. H. (2020, February). The facts about Parkinson's Disease. Harvard Health. https://www.health.harvard.edu/diseases-and-conditions/the-facts-about-parkinsons-disease

6. The Genetic Link to Parkinson's Disease. (n.d.). Www.hopkinsmedicine.org. https://www.hopkinsmedicine.org/health/conditions-and-diseases/parkinsons-disease/the-genetic-link-to-parkinsons-disease

7. Tolosa, E., Garrido, A., Scholz, S. W., & Poewe, W. (2021). Challenges in the diagnosis of Parkinson's disease. The Lancet Neurology, 20(5), 385–397. https://doi.org/10.1016/S1474-4422(21)00030-2

_By: Annika Thakur_

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of Elio Academy.