|
The content on or accessible through Medpedia.com is for informational purposes only. Medpedia is not a substitute for professional advice or expert medical services from a qualified health professional.
Read more
|
Synuclein, alpha (non A4 component of amyloid precursor) (SNCA)
There are currently no Lead Editors of this article.
Ask a Question on This Topic
Important Resources for Synuclein, alpha (non A4 component of amyloid precursor) (SNCA):
The information on this page is seed content provided by an organization. Please help improve this Article by adding to it. If you are a physician or PhD, learn how to edit. If you are anyone else, learn how to suggest changes.
The official name of this gene is “synuclein, alpha (non A4 component of amyloid precursor).”
SNCA is the gene's official symbol. The SNCA gene is also known by other names, listed below.
What is the normal function of the SNCA gene?
The SNCA gene provides instructions for making a small protein called alpha-synuclein. Alpha-synuclein is abundant in the brain, and smaller amounts are found in the heart, muscles, and other tissues. In the brain, alpha-synuclein localizes mainly at the tips of nerve cells (neurons) in specialized structures called presynaptic terminals. Within these structures, alpha-synuclein interacts with fats (lipids) and other proteins. Presynaptic terminals release chemical messengers, called neurotransmitters, from compartments known as synaptic vesicles.
Although the function of alpha-synuclein remains unknown, several studies suggest that it plays an important role in maintaining a supply of synaptic vesicles in presynaptic terminals. It may also help regulate the release of dopamine. Dopamine is a type of neurotransmitter that is critical for controlling the start and stop of voluntary and involuntary movements.
How are changes in the SNCA gene related to health conditions?
Parkinson disease - caused by mutations in the SNCA gene
- Researchers have described two types of alterations of the SNCA gene that cause early-onset Parkinson disease. One type of alteration changes one of the protein building blocks (amino acids) used to make alpha-synuclein. In some cases, the amino acid alanine is replaced with the amino acid threonine at protein position 53 (written as Ala53Thr) or with the amino acid proline at position 30 (written as Ala30Pro). In a few cases, the amino acid glutamic acid is replaced with the amino acid lysine at position 46 (written as Glu46Lys). These mutations cause the alpha-synuclein protein to misfold, or take on an incorrect 3-dimensional shape. In the other type of alteration, one of the two SNCA genes in each cell is inappropriately duplicated or triplicated. Instead of the normal two copies of the SNCA gene, each cell has three or four copies, which leads to an excess amount of alpha-synuclein.
- It is not clearly understood how alterations of the SNCA gene cause Parkinson disease, which is characterized by the selective death or impairment of neurons that produce dopamine. Mutated or excess alpha-synuclein proteins may cluster together (aggregate) and impair neuron functions in specific regions of the brain. For example, aggregated alpha-synuclein may disrupt the regulation of dopamine, which allows dopamine to accumulate to toxic levels and eventually kill the nerve cell. Researchers also suspect that misfolded or excess alpha-synuclein stalls or shuts down the cell machinery that removes unwanted proteins. As a result, unwanted proteins may clog the cell and impair neuron functions. Symptoms of Parkinson disease appear as an increased number of dopamine-producing neurons are impaired or die.
- Misfolded alpha-synuclein is also a major component of Lewy bodies, abnormal deposits that appear in certain nerve cells in the brain. Lewy bodies in a region of the brain called the substantia nigra, which controls balance and movement, are a characteristic feature of Parkinson disease.
other disorders - caused by mutations in the SNCA gene
- Researchers have identified mutations in the SNCA gene that may lead to a loss of intellectual functions (dementia). Two mutations cause a particular disorder known as dementia with Lewy bodies, in which dementia is associated with deposits of Lewy bodies in certain areas of the brain. Although the features of this disorder are variable, symptoms typically include dementia, visual hallucinations, fluctuations in attention, and changes characteristic of Parkinson disease such as trembling or rigidity of limbs, slow movement, and impaired balance and coordination.
- One of the SNCA mutations responsible for dementia with Lewy bodies replaces the amino acid glutamic acid with the amino acid lysine at position 46 in the alpha-synuclein protein (written as Glu46Lys). The other mutation, which replaces the amino acid alanine with the amino acid threonine at position 53 (written as Ala53Thr), is associated with the features of both Parkinson disease and dementia with Lewy bodies.
Where is the SNCA gene located?
Cytogenetic Location: 4q21
Molecular Location on chromosome 4: base pairs 90,865,727 to 90,977,155
The SNCA gene is located on the long (q) arm of chromosome 4 at position 21.
More precisely, the SNCA gene is located from base pair 90,865,727 to base pair 90,977,155 on chromosome 4.
What other names do people use for the SNCA gene or gene products?
- alpha-synuclein
- NACP
- nonA-beta component of AD amyloid
- PARK1
- PARK4
- PD1
- SYUA_HUMAN
Where can I find additional information about SNCA?
You and your healthcare professional may find the following resources about SNCA helpful.
- Educational resources - Information pages
- Basic Neurochemistry (sixth edition, 1999): Composition of Synaptic Vesicles (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=bnchm.section.639)
- Molecular Cell Biology (fourth edition, 2000): Neurotransmitters, Synapses, and Impulse Transmission (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mcb.section.6187)
- National Institute of Neurological Disorders and Stroke: Dementia with Lewy Bodies (http://www.ninds.nih.gov/disorders/dementiawithlewybodies/dementiawithlewybodies.htm)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=((SNCA[TIAB])+OR+(alpha-synuclein[TIAB]))+AND+((Genes[MH])+OR+(Genetic+Phenomena[MH]))+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=360+Days)
- OMIM - Genetic disorder catalog
- OMIM: Lewy Body Dementia (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=127750)
- OMIM: SNCA (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163890)
- Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_SNCA.html)
- Entrez Gene (http://view.ncbi.nlm.nih.gov/gene/6622)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?gene=SNCA)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=11138)
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding SNCA?
acids ; aggregate ; amino acid ; amyloid ; cell ; dementia ; dopamine ; gene ; hallucinations ; involuntary ; Lewy bodies ; lipid ; mutation ; nerve cell ; neuron ; neurotransmitters ; presynaptic ; protein ; substantia nigra ; symptom ; synaptic vesicles ; threonine ; tissue ; toxic ; vesicle
References
- Abou-Sleiman PM, Muqit MM, Wood NW. Expanding insights of mitochondrial dysfunction in Parkinson's disease. Nat Rev Neurosci. 2006 Mar;7(3):207-19. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16495942)
- Bonini NM, Giasson BI. Snaring the function of alpha-synuclein. Cell. 2005 Nov 4;123(3):359-61. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16269324)
- Cookson MR. The biochemistry of Parkinson's disease. Annu Rev Biochem. 2005;74:29-52. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15952880)
- Farrer M, Kachergus J, Forno L, Lincoln S, Wang DS, Hulihan M, Maraganore D, Gwinn-Hardy K, Wszolek Z, Dickson D, Langston JW. Comparison of kindreds with parkinsonism and alpha-synuclein genomic multiplications. Ann Neurol. 2004 Feb;55(2):174-9. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14755720)
- Gasser T. Genetics of Parkinson's disease. Curr Opin Neurol. 2005 Aug;18(4):363-9. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16003110)
- Golbe LI, Mouradian MM. Alpha-synuclein in Parkinson's disease: light from two new angles. Ann Neurol. 2004 Feb;55(2):153-6. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14755715)
- Hardy J, Cai H, Cookson MR, Gwinn-Hardy K, Singleton A. Genetics of Parkinson's disease and parkinsonism. Ann Neurol. 2006 Oct;60(4):389-98. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=17068789)
- Lim KL, Dawson VL, Dawson TM. The cast of molecular characters in Parkinson's disease: felons, conspirators, and suspects. Ann N Y Acad Sci. 2003 Jun;991:80-92. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12846976)
- Morfis L, Cordato DJ. Dementia with Lewy bodies in an elderly Greek male due to alpha-synuclein gene mutation. J Clin Neurosci. 2006 Nov;13(9):942-4. Epub 2006 Oct 16. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=17049244)
- Morris HR. Genetics of Parkinson's disease. Ann Med. 2005;37(2):86-96. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16026116)
- Norris EH, Giasson BI, Lee VM. Alpha-synuclein: normal function and role in neurodegenerative diseases. Curr Top Dev Biol. 2004;60:17-54. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15094295)
- OMIM: SNCA (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163890)
- Pandey N, Schmidt RE, Galvin JE. The alpha-synuclein mutation E46K promotes aggregation in cultured cells. Exp Neurol. 2006 Feb;197(2):515-20. Epub 2005 Dec 1. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16325180)
- Pankratz N, Foroud T. Genetics of Parkinson Disease. Neurorx. 2004 Apr;1(2):235-242. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15717024)
- Sidhu A, Wersinger C, Vernier P. alpha-Synuclein regulation of the dopaminergic transporter: a possible role in the pathogenesis of Parkinson's disease. FEBS Lett. 2004 May 7;565(1-3):1-5. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15135042)
- Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K. alpha-Synuclein locus triplication causes Parkinson's disease. Science. 2003 Oct 31;302(5646):841. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14593171)
- Tan EK, Skipper LM. Pathogenic mutations in Parkinson disease. Hum Mutat. 2007 Mar 26; [Epub ahead of print]. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=17385668)
- Tofaris GK, Spillantini MG. Alpha-synuclein dysfunction in Lewy body diseases. Mov Disord. 2005 Aug;20 Suppl 12:S37-44. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16092089)
- Zarranz JJ, Alegre J, Gomez-Esteban JC, Lezcano E, Ros R, Ampuero I, Vidal L, Hoenicka J, Rodriguez O, Atares B, Llorens V, Gomez Tortosa E, del Ser T, Munoz DG, de Yebenes JG. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol. 2004 Feb;55(2):164-73. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14755719)
To suggest changes to this page, you must create an account on Medpedia.
