This paper provides a comprehensive overview of Parkinson's disease, the second most prevalent neurological disorder worldwide. It examines the neurological basis of the disease, including the degeneration of dopamine-producing nerve cells in the substantia nigra and the resulting motor and cognitive symptoms. The paper discusses both sporadic and hereditary forms of the disease, detailing autosomal dominant and autosomal recessive inheritance patterns involving genes such as LRRK2, SNCA, PARK2, PARK7, and PINK1. It also covers diagnostic approaches, current treatment options including medication, physical therapy, and deep brain stimulation, and addresses the ethical controversy surrounding stem cell transplantation as a potential cure.
Parkinson's disease is a neurological disorder that has become the subject of much research in recent years. This disease affects more than four million individuals around the world, making it the second most prevalent neurological disorder (National Institute of Health, 2013). The United States alone records about 60,000 new diagnoses every year. Parkinson's disease can affect an individual of any age; however, the form most familiar to the general public is late-onset Parkinson's disease, which encompasses those older than 55 years. Young-onset, or early-onset, Parkinson's disease affects individuals before the age of 50, while juvenile-onset Parkinson's disease affects those under the age of 20 (NHGRI, 2011). Regardless of the age at which the disease first appears, its devastating effects are the same.
The symptoms of this disorder create great disruption in the affected individual's life. Parkinson's disease causes the degeneration of nerve cells directly connected to a region in the mesencephalon, or midbrain. The specific area, called the substantia nigra, is responsible for coordinating and controlling an individual's balance and movement (National Institute of Health, 2013). This accounts for the shaking or trembling most commonly associated with the disease. The function of these nerve cells depends on the ability of the neurotransmitter dopamine to cross the synaptic cleft of neurons. As these nerve cells begin to degenerate, the signals that dopamine is supposed to transmit to other nerve cells either fail to reach their target or are drastically slowed (National Institute of Health, 2013). This typically occurs while the body is at rest, and the shaking can affect the muscles of the limbs — including the legs, feet, arms, and hands — as well as the face (Talan, 2012). Symptoms appear early in the disease and worsen progressively until nearly all functionality is diminished. The defining characteristic of these symptoms is the individual's inability to control the jerky, trembling motions.
Although Parkinson's disease is most recognized for causing tremors, there are numerous less widely known symptoms. Because dopamine plays a critical role in nerve cell innervation, stiffness and rigidity can develop, along with bradykinesia, or abnormally slow movement. As nerve fibers continue to deteriorate, signals to the parts of the brain that control movement are drastically slowed, to the point where akinesia — the complete inability to move — may also develop (National Institute of Health, 2013). Proper posture, balance, and coordination are diminished as the disease progresses. Because Parkinson's disease directly affects the brain, psychiatric and cognitive abilities are also greatly reduced. Many affected individuals develop depression and dementia, and may experience hallucinations. These conditions all contribute to deteriorating memory and impaired judgment.
The symptoms of Parkinson's disease are devastating for those afflicted, and depending on the age of onset, the effects can be particularly severe. Parkinson's disease is considered "sporadic" when it occurs in an individual with no family history of the disease, suggesting that environmental factors may be responsible for its onset (NHGRI, 2011). However, the most common characteristic of Parkinson's disease is its tendency to appear repeatedly within families, suggesting a significant genetic component. The mode of inheritance depends on which chromosomal genes are involved. It can be either autosomal recessive or autosomal dominant (NHGRI, 2011). In the autosomal recessive pattern, an affected individual must inherit two mutated recessive alleles — one from each parent — in order to develop the disease. In the autosomal dominant pattern, inheriting just one mutated allele is sufficient to cause the disease.
A mutation is associated with the malfunction of nerve cells in the brain. The chromosomal genes that have been identified as mutated in Parkinson's disease include: LRRK2, SNCA, PARK2, PARK7, VPS35, UCHL1, GBA, PINK1, and ATP13A2 (National Institute of Health, 2013). Although the exact mechanisms that lead to mutations in these genes are not fully understood, it is believed that the LRRK2 and/or SNCA gene on chromosome 6 is inherited in a dominant pattern, while mutations in the PARK2, PARK7, and/or PINK1 gene on chromosome 4 result in an autosomal recessive mode of inheritance (National Institute of Health, 2013). The Punnett squares below illustrate these patterns of inheritance and the associated probabilities for offspring:
Dominant autosomal (both parents affected, homozygous): 100% chance of offspring being affected by Parkinson's disease.
Recessive autosomal (both parents carriers): 100% chance of offspring being a carrier of the mutation; 0% chance of being affected.
Dominant autosomal (one parent homozygous affected, one unaffected): 75% chance of offspring being affected; 25% chance of offspring being unaffected.
Recessive autosomal (one parent carrier, one parent affected): 50% chance of offspring being a carrier; 25% chance of being unaffected; 25% chance of being affected.
Dominant autosomal (one parent heterozygous affected, one affected): 100% chance of offspring being affected.
Recessive autosomal (one parent carrier, one parent unaffected): 50% chance of offspring being unaffected; 50% chance of offspring being a carrier for the mutation.
"Diagnostic methods and role of family history"
"Medications, physical therapy, and brain stimulation"
"Moral debate over stem cell transplantation as cure"
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