Assignment 1: A gene for Parkinson's Disease?
Parkinson's Disease Alpha-synuclein Popular Press vs. Scientific Press Relative Links
Figure 1. This picture illustrates human 4. Note the approximate
location of the alpha-synuclein gene (SNCA) on chromosome 4 as denoted
by the bracket. Original image can be found at NCBI.
requested from NCBI.
Parkinson's Disease is a neurological disorder characterized by limb tremors,
slow or no movement, stiff limbs, shuffling walk, and a stooped posture.
Other symptoms may include depression, personality changes, dementia, sleep
disturbances, speech impariments, or sexual difficulties. These conditions
progressively become more severe. Onset of Parkinson's Disease occurs
around age 60 (http://www.nhgri.nih.gov/DIR/LGDR/PARK/about_parks.html).
These symptoms are a result of neuronal degeneration in the portion of the brain controlling motor skills. The degenerated neurons lead to a lack of the neurotransmitter, dopamine, and thus an action potential is not generated and impulses cannot be exchanged between sensory receptors and other neurons. When the brain and a body's muscles do not jive, motor skills become severely impaired.
Parkinson's Disease is thought to have both genetic and environmental causes. Familial Parkinson's Disease was first discovered in an Italian family with a defective alpha-synuclein gene. China has a high incidence of early-onset Parkinson's Disease that is postulated to be a result of a mutation in the parkin gene. One environmental factor is the result of taking an illegal drug contaminated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). A second environmental factor has been identified in individuals who experienced a severe case of influenza during the early twentieth century epidemic (http://www.nhgri.nih.gov/DIR/LGDR/PARK2/media_release.html).
Alpha-synuclein is part of the synuclein family including beta- and gamma-synuclein.
Synoretin is the most recently cloned synulcein and can be found in the
Synucleins are very common in the brain. SNCA located on chrmosome
4 expresses the140-amino acid protein alpha-synuclein (OMIM*163890).
Figure 2. This amino acid sequence aligns the human synuclein proteins. The highlighted regions indicated sequences conserved throughout the four proteins. KTKEGV imperfect repeats are indicated. Original figure and additional explanation are located at http://health.upenn.edu/cndr/research1/tausyn/tausyn.htm. Permission requested from the University of Pennsylvania Health System.
It is thought that the mutant forms of alpha-nuclein aggregate and induce other proteins to incorporate into the aggregate as well. These aggregates are known as Lewy bodies and are comprised primarily of alpha-synuclein. Lewy bodies are similar to the beta-amyloid plaques found in Alzheimer's patients. In fact, alpha-synuclein is also the largest component of these Alzheimer-related plaques (http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=6622). The Lewy bodies lead to loss of neurons, then dopamine (a neurotransmitter), and finally loss of motor control. Additionally, the absence of alpha-synuclein in neurofibrillary tangles has been implicated in Alzheimer's disease, Pick's disease, Progressive Supranuclear Palsy, and Corticobasal Degeneration (http://www.cnn.com/HEALTH/9611/14/nfm/parkinsons/index.html).
Figure 3. This Lewy body shows the presence of alpha-synuclein in red. Original image can be found at NCBI. Permission requested from NCBI.
Popular Press vs. Scientific Press
According to CNN, scientists "cracked the mystery
of Parkinson's Disease" when a gene was located on the long arm of chromosome
four in 1996. It's exact location was unknown, but the fact that
Parkinson's Disease had a genetic component was "heralded as a breakthrough."
CNN's news release indicated that this discovery would lead to a treatment
for this disease that afflicts "as many as 1.5 million Americans" (http://www.cnn.com/HEALTH/9611/14/nfm/parkinsons/index.html).
On June 27, 1997, Michel Polymeropoulos found that SNCA was the gene responsible for Parkinson's Disease in an Italian family. He noted that alpha-synuclein (SNCA's polypeptide) was "first isolated from plaques found in patients with Alzheimer's Disease." He pointed out that a mutated SNCA was "unlikely to account for the majority of sporadic and familial cases of PD." Polymeropoulos was optimistic that this discovery would "lead to the understanding of the underlying pathways resulting in the symptoms of PD" (Polymeropoulos 1997)).
TIME magazine reported on January 15, 2001 that a new gene, the parkin gene, was defective in many more cases of familial Parkinson's Disease and that the SNCA mutation was very rare. They also said that early-onset- PD was carried on a recessive gene, whereas Polymeropoulos said that the condition resulted from a dominant allele (Kluger 2001).
Initially, the scientific community and the popular press seemed to interpret the discovery of a "Parkinson's gene" in the same way. The media did use more extreme flamboyant words to describe the event, whereas the scientists took a more conservative approach, but essentially both communities thought that the discovery of SNCA might lead to a better understanding of the mechanisms behind Parkinson's Disease. Later on, the popular press began to denounce the importance of this discovery, citing the rarity of an SNCA mutation in persons with PD. The scientific community continued to study SNCA, but in the context of its relationship with ubiquitin and parkin (a protein and a gene that interact with alpha-synuclein). However, both communities continue to agree about the importance of SNCA in gaining a deeper understanding of Parkinson's Disease.
The Parkinson's Web - includes information on national Parkinson's Disease organizations, private centers and foundations, governmental resources, patient and family support, medcal centers, neurosurgical centers, neurological organizations, and Parkinson's Disease advocacy organizations
Parkinson's Disease Foundation, Inc. - discusses Parkinson's Disease and the various events that the organization has planned
The National Parkinson Foundation - includes a library, a forum to ask questions regarding the disease, and information regarding grants and studies
NCBI - gives a brief synopsis of Parkinson's Disease including origin of its name and genetic causes
of Intramural Research - provides background information
regarding Parkinson's Disease
2001 Apr. NIH Researchers Find First Parkinson's
Disease Gene. Division of Intramural Research, NHGRI.
<http://www.nhgri.nih.gov/DIR/LGDR/PARK2/media_release.html> Accessed 2001 2 Sept.
2001 Apr. Research News: Parkinson's Disease.
Division of Intramural Research, NHGRI. <http://www.nhgri.nih.gov/DIR/LGDR/PARK/about_parks.html>
Accessed 2001 2 Sept.
2001 Aug. Alpha-Synuclein Polyclonal Antibody. Chemicon. <http://www.chemicon.com/litlibrary/PR/synucpr.htm> Accessed 2001 12 Sept.
Giasson BI et al. 1999 Sept. Tau and alpha-Synuclein
Dysfunction and Aberrant Aggregates Define Distinct Neurodegenerative Diseases.
Pennsylvania Health System Center for Neurodegenerative Disease Research. <http://health.upenn.edu/cndr/research1/tausyn/tausyn.htm> Accessed 2001
Kluger J. 2001. Lubricating Gummed-Up Brains. TIME 157(2):86&89.
Levine J. 1996 Nov. Scientists identify genetic
cause for Parkinson's Disease. CNN Health.
<http://www.cnn.com/HEALTH/9611/14/nfm/parkinsons/index.html> Accessed 2001 Sept 3.
Polymeropoulos MH, et al. 1997. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276(5321):2045-7.
Unknown. SNCA: synuclein, alpha (non A4 component
of amyloid precursor) Locus ID:6622. NCBI LocusLink.
<http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=6622> Accessed 2001 2 Sept.
Unknown. Synuclein, Alpha; SNCA *163890. Online
Mendelian Inheritance in Man. <http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?163890>
Accessed 2001 2 Sept.
Xia Y, et al. 2001. Characterization of the human
NACP/alpha-Synuclein (SNCA) gene: genomic structure, transcription start
site, promoter region and
polymorphisms. Journal of Alzheimer's Disease 3(5).
Genomics Web Page