Editing Alpha-synuclein (section)

{{Short description|Protein found in humans}}
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{{Infobox gene}}
'''Alpha-synuclein''' ('''aSyn''') is a [[protein]] that in humans is encoded by the ''SNCA'' [[gene]].<ref name="ghrsnca">{{cite web | work = Genetics Home Reference | title = SNCA | date = 12 Nov 2013 | url = http://ghr.nlm.nih.gov/gene/SNCA | publisher = U.S. National Library of Medicine | access-date = 14 Nov 2013 }}</ref> It is a neuronal protein involved in the regulation of [[synaptic vesicle trafficking]] and the release of [[neurotransmitter]]s.<ref name="Bonini_2005" /><ref name="Chandra_2005" />

Alpha-synuclein is abundant in the brain, with smaller amounts present in the heart, muscles, and other tissues. Within the brain, it is primarily localized to the [[axon terminal]]s of [[presynaptic neuron]]s.<ref name="ghrsnca" /> There, it interacts with [[phospholipid]]s<ref>{{cite journal | vauthors = Chandra S, Chen X, Rizo J, Jahn R, Südhof TC | title = A broken alpha -helix in folded alpha -Synuclein | journal = The Journal of Biological Chemistry | volume = 278 | issue = 17 | pages = 15313–15318 | date = April 2003 | pmid = 12586824 | doi = 10.1074/jbc.M213128200 | s2cid = 27116894 | doi-access = free }}</ref> and other proteins.<ref name="ghrsnca" /><ref name="Sun_2019" /><ref>{{cite journal | vauthors = Atias M, Tevet Y, Sun J, Stavsky A, Tal S, Kahn J, Roy S, Gitler D | title = Synapsins regulate α-synuclein functions | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 23 | pages = 11116–11118 | date = June 2019 | pmid = 31110014 | pmc = 6561288 | doi = 10.1073/pnas.1903054116 | bibcode = 2019PNAS..11611116A | doi-access = free }}</ref> Presynaptic terminals release neurotransmitters from specialized compartments called [[synaptic vesicle]]s, a process essential for neuronal communication and normal brain function.<ref name="ghrsnca" />

In [[Parkinson's disease]] and related [[synucleinopathies]], abnormal, insoluble forms of alpha-synuclein accumulate within neurons as [[inclusion bodies|inclusions]] known as [[Lewy body|Lewy bodies]].<ref>{{cite journal | vauthors = Spillantini MG, Schmidt ML, Lee VM, Trojanowkski JQ, Jakes R, Goedert M | title = α-Synuclein in Lewy bodies | journal = Nature | volume = 388 | issue = 6645 | pages = 839–840 | date = 28 August 1997 | pmid = 9278044 | doi = 10.1038/42166 | bibcode = 1997Natur.388..839G | s2cid = 4419837 | doi-access = free }}</ref>
Mutations in the ''SNCA'' gene are linked to familial forms of Parkinson's disease. During the process of seeded nucleation, alpha-synuclein adopts a cross-beta sheet structure characteristic of [[amyloid]] fibrils.<ref name="Zigmond_2015">{{cite book | vauthors = Zigmond MJ, Coyle JT, Rowland JP | title = Neurobiology of brain disorders : biological basis of neurological and psychiatric disorders | location = London | publisher = Academic Press | date = 2015 | url = https://www.worldcat.org/oclc/896232309 | isbn = 978-0-12-398280-3 | oclc = 896232309 }}</ref>

The human alpha-synuclein protein consists of 140 amino acids.<ref name="Ueda_1993">{{cite journal | vauthors = Uéda K, Fukushima H, Masliah E, Xia Y, Iwai A, Yoshimoto M, Otero DA, Kondo J, Ihara Y, Saitoh T | title = Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 23 | pages = 11282–11286 | date = December 1993 | pmid = 8248242 | pmc = 47966 | doi = 10.1073/pnas.90.23.11282 | doi-access = free | bibcode = 1993PNAS...9011282U }}</ref><ref name="Xia_2001">{{cite journal | vauthors = Xia Y, Saitoh T, Uéda K, Tanaka S, Chen X, Hashimoto M, Hsu L, Conrad C, Sundsmo M, Yoshimoto M, Thal L, Katzman R, Masliah E | title = Characterization of the human alpha-synuclein gene: Genomic structure, transcription start site, promoter region and polymorphisms | journal = Journal of Alzheimer's Disease | volume = 3 | issue = 5 | pages = 485–494 | date = October 2001 | pmid = 12214035 | doi = 10.3233/JAD-2001-3508 | url = http://iospress.metapress.com/content/jpmvj4dubjpm3b73/ | access-date = 2009-02-19 | url-status = dead | archive-url = http://arquivo.pt/wayback/20160514170300/http://iospress.metapress.com/content/jpmvj4dubjpm3b73/ | archive-date = 2016-05-14 }}</ref><ref>{{cite journal | vauthors = Xia Y, Saitoh T, Uéda K, Tanaka S, Chen X, Hashimoto M, Hsu L, Conrad C, Sundsmo M, Yoshimoto M, Thal L, Katzman R, Masliah E | title = Characterization of the human alpha-synuclein gene: Genomic structure, transcription start site, promoter region and polymorphisms: Erratum p489 Fig 3 | journal = J. Alzheimer's Dis. | volume = 4 | issue = 4 | pages = 337 | year = 2002 | url = http://iospress.metapress.com/content/jpmvj4dubjpm3b73/ | archive-url = http://arquivo.pt/wayback/20160514170300/http://iospress.metapress.com/content/jpmvj4dubjpm3b73/ | url-status = dead | archive-date = 2016-05-14 | access-date = 2009-02-19 }}</ref> A fragment of alpha-synuclein, known as the non-[[amyloid beta]] component (NAC) of [[Alzheimer's disease]] [[amyloid]], was initially isolated from an amyloid-rich brain fraction and shown to derive from a precursor protein named NACP.<ref name="Ueda_1993" /> NACP was subsequently identified as the human homologue of synuclein from the electric ray genus ''[[Torpedo (genus)|Torpedo]]'', leading to its renaming as human alpha-synuclein.<ref name="Jakes_1994">{{cite journal | vauthors = Jakes R, Spillantini MG, Goedert M | title = Identification of two distinct synucleins from human brain | journal = FEBS Letters | volume = 345 | issue = 1 | pages = 27–32 | date = May 1994 | pmid = 8194594 | doi = 10.1016/0014-5793(94)00395-5 | s2cid = 36840279 | doi-access = free | bibcode = 1994FEBSL.345...27J }}</ref>