Alpha-synuclein
Alpha-synuclein (aSyn) is a protein that in humans is encoded by the SNCA gene.[5] It is a neuronal protein involved in the regulation of synaptic vesicle trafficking and the release of neurotransmitters.[6][7]
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 terminals of presynaptic neurons.[5] There, it interacts with phospholipids[8] and other proteins.[5][9][10] Presynaptic terminals release neurotransmitters from specialized compartments called synaptic vesicles, a process essential for neuronal communication and normal brain function.[5]
In Parkinson's disease and related synucleinopathies, abnormal, insoluble forms of alpha-synuclein accumulate within neurons as inclusions known as Lewy bodies.[11] 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.[12]
The human alpha-synuclein protein consists of 140 amino acids.[13][14][15] 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.[13] NACP was subsequently identified as the human homologue of synuclein from the electric ray genus Torpedo, leading to its renaming as human alpha-synuclein.[16]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000145335 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025889 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d "SNCA". Genetics Home Reference. U.S. National Library of Medicine. 12 Nov 2013. Retrieved 14 Nov 2013.
- ^ Cite error: The named reference
Bonini_2005was invoked but never defined (see the help page). - ^ Cite error: The named reference
Chandra_2005was invoked but never defined (see the help page). - ^ Chandra S, Chen X, Rizo J, Jahn R, Südhof TC (April 2003). "A broken alpha -helix in folded alpha -Synuclein". The Journal of Biological Chemistry. 278 (17): 15313–15318. doi:10.1074/jbc.M213128200. PMID 12586824. S2CID 27116894.
- ^ Cite error: The named reference
Sun_2019was invoked but never defined (see the help page). - ^ Atias M, Tevet Y, Sun J, Stavsky A, Tal S, Kahn J, et al. (June 2019). "Synapsins regulate α-synuclein functions". Proceedings of the National Academy of Sciences of the United States of America. 116 (23): 11116–11118. Bibcode:2019PNAS..11611116A. doi:10.1073/pnas.1903054116. PMC 6561288. PMID 31110014.
- ^ Spillantini MG, Schmidt ML, Lee VM, Trojanowkski JQ, Jakes R, Goedert M (28 August 1997). "α-Synuclein in Lewy bodies". Nature. 388 (6645): 839–840. Bibcode:1997Natur.388..839G. doi:10.1038/42166. PMID 9278044. S2CID 4419837.
- ^ Zigmond MJ, Coyle JT, Rowland JP (2015). Neurobiology of brain disorders : biological basis of neurological and psychiatric disorders. London: Academic Press. ISBN 978-0-12-398280-3. OCLC 896232309.
- ^ a b Uéda K, Fukushima H, Masliah E, Xia Y, Iwai A, Yoshimoto M, et al. (December 1993). "Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease". Proceedings of the National Academy of Sciences of the United States of America. 90 (23): 11282–11286. Bibcode:1993PNAS...9011282U. doi:10.1073/pnas.90.23.11282. PMC 47966. PMID 8248242.
- ^ Xia Y, Saitoh T, Uéda K, Tanaka S, Chen X, Hashimoto M, et al. (October 2001). "Characterization of the human alpha-synuclein gene: Genomic structure, transcription start site, promoter region and polymorphisms". Journal of Alzheimer's Disease. 3 (5): 485–494. doi:10.3233/JAD-2001-3508. PMID 12214035. Archived from the original on 2016-05-14. Retrieved 2009-02-19.
- ^ Xia Y, Saitoh T, Uéda K, Tanaka S, Chen X, Hashimoto M, et al. (2002). "Characterization of the human alpha-synuclein gene: Genomic structure, transcription start site, promoter region and polymorphisms: Erratum p489 Fig 3". J. Alzheimer's Dis. 4 (4): 337. Archived from the original on 2016-05-14. Retrieved 2009-02-19.
- ^ Jakes R, Spillantini MG, Goedert M (May 1994). "Identification of two distinct synucleins from human brain". FEBS Letters. 345 (1): 27–32. Bibcode:1994FEBSL.345...27J. doi:10.1016/0014-5793(94)00395-5. PMID 8194594. S2CID 36840279.