What is Parkinson's Disease?
Parkinson's Disease (PD) is the second most common neurodegenerative disease [10]. Around 930,000 people in the U.S. and 10 million people worldwide are diagnosed with PD. In the U.S., 60,000 people are diagnosed with PD a year [9].
The number of people living with PD in the U.S. is expected to increase 29% between 2020 and 2030. |
PD is caused by the breakdown of dopamine neurons in a part of the brain called the substantia nigra.[6] The substantia nigra is apart of the nigrostriatal dopamine pathway, which is important for movement.[4] As more dopamine neurons breakdown and die, PD symptoms develop and progress. In brain scans, the substantia nigra is noticeably less visible in PD patients because of the decrease in dopamine neurons [6].
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Symptoms of PD |
There are three main symptoms that people think of when they hear Parkinson's.
Click the images to see and hear about real life examples.
Click the images to see and hear about real life examples.
However, no one person with PD experiences the same symptoms. In fact, there's a quote among many movement motor specialists:
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"If you've met someone with Parkinson's, you have met one person with Parkinson's" |
75% |
Of people with Parkinson's report experiencing sleeping problems.
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Stages of PD [8] |
There are five stages of PD that scale with symptom severity.
Stage 1
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Stage 2
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Stage 3
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Stage 4
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Stage 5
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Different stages of PD can affect therapeutic treatments such as the type of medication, the dosage of medications and physical therapy.
Risk Factors of PD [2] |
Scientist recognize there are two factors that combine to cause PD.
Environmental Factors
Environmental factors are situations in a person's life that increased or decreased the likelihood of developing PD. Some common environmental factors are head injuries and exposure to chemicals. Males are also more likely to develop PD than women. However, the most common environmental factor is age. The average onset of PD is 60, with 1% of people over the age of 60 having PD.
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Genetic Factors
Genetic factors are the risks of developing PD based on someone's DNA. A person's DNA contains different genes that make someone who they are. Slight changes in genes are what cause people to be different from one another. Genes are often passed down from parents to their children. Sometimes, these changes can be detrimental to a person's health. There is evidence to show that mutations, or changes, in specific genes are associated with an increased risk of PD. It's estimated that 10%-15% of all PD cases are passed down from family members. One of the most common mutations that is associated with PD is in the LRRK2 gene, which is found in about 1%-2% of all PD patients. [3]
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What is LRRK2?
As the name implies, the human leucine-rich-repeat kinase 2 (LRRK2) is a kinase. Kinases are enzymes that speed up the process of cellular functions. By adding a phosphate group to other molecules, kinases can either increase or decrease the activity of the molecule.
LRRK2 is complicated and has many functions in a cell. LRRK2 is also called PARK8 and produces a protein commonly called dardarin. The leucine-rich-repeat (LRR) section of the gene indicates that this protein interacts with other proteins, possibly in the cytoskeleton of the cell and in the membrane of the mitochondria [7]. There's evidence that LRRK2 is associated with neuron growth and branching. However, the mechanism of how it does this is still unknown [5]. Abnormal LRRK2 has also been shown to affect a cell's ability to know when it needs to die. Cells can usually detect when there is a problem with them and can self-destruct, or perform apoptosis. LRRK2 mutations have affected this process and prevented cells from going through apoptosis [5].
LRRK2 and PD |
Currently, scientists know over 100 mutations associated with PD in LRRK2 [7]. Most mutations that result in PD cause an increase in LRRK2 kinase activity [5]. The most common mutation that is associated with PD is G2019S. In certain populations such as Ashkenazi Jews, the G2019S mutation is found in 30%-40% of people and has subsequently shown an increase in the prevalence of PD [3]. Therapeutic medication is being developed to inhibit LRRK2 kinase activity. However, because LRRK2 has many functions around the cell, it has been difficult to find a way to inhibit the kinase activity without negatively affecting the cell [5].
Gap in KnowledgeCurrently, it is unknown how or if LRRK2 affects the circadian rhythm. Understanding this could help bring therapeutic relief to the 75% of people diagnosed with Parkinson's who report having sleeping problems. |
This website was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison
References
[1] 10 early signs of Parkinson's disease. https://www.parkinson.org/understanding-parkinsons/10-early-warning-signs. [2] Causes. https://www.parkinson.org/Understanding-Parkinsons/Causes. [3] Common genetic mutations. https://www.parkinson.org/understanding-parkinsons/causes/genetics/common-genetic-mutations. [4] Dingman, M. (2014, November 15). Know your brain: Substantia nigra. https://www.neuroscientificallychallenged.com/blog/know-your-brain-substantia-nigra. [5] Ho, F. Y., Rosenbusch, K. E., & Kortholt, A. (2014, March 26). The potential of targeting LRRK2 in Parkinson's disease. https://www.intechopen.com/books/a-synopsis-of-parkinson-s-disease/the-potential-of-targeting-lrrk2-in-parkinson-s-disease. [6] Ju, W., Santos, A., Freeman, A., & Daniele, E. (2018). 2.4 Chronic Neurodegenerative Diseases. In Neuroscience (1st ed.). eCampusOntario. http://neuroscience.openetext.utoronto.ca/. [7] LRRK2 gene. (2020, August 18). https://medlineplus.gov/genetics/gene/lrrk2/#conditions. [8] Stages of Parkinson's. https://www.parkinson.org/Understanding-Parkinsons/What-is-Parkinsons/Stages-of-Parkinsons. [9] Statistics. https://www.parkinson.org/Understanding-Parkinsons/Statistics. [10] What is Parkinson's? https://www.parkinson.org/understanding-parkinsons/what-is-parkinsons. |
Image References
*Images are hyperlinked to source unless stated below Header: https://www.agedcareguide.com.au/talking-aged-care/30m-parkinsons-funding-most-significant-in-australian-history Shaking Hands: https://www.news-medical.net/health/Types-of-movement-disorders.aspx Stiff Shoulder: https://www.hiclipart.com/free-transparent-background-png-clipart-ijjjq Man Buttoning Shirt: https://newsinhealth.nih.gov/2015/08/all-about-als Symptoms: https://sites.google.com/site/activecarephysiotherapyclinic/parkinsons-disease |