Beta-synuclein
Protein-coding gene in the species Homo sapiens
Beta-synuclein is a protein that in humans is encoded by the SNCB gene .[ 5] [ 6] [ 7]
The protein encoded by this gene is highly homologous to alpha-synuclein . These proteins are abundantly expressed in the brain and putatively inhibit phospholipase D2 selectively. The encoded protein, which may play a role in neuronal plasticity, is abundant in neurofibrillary lesions of patients with Alzheimer's disease . This protein has been shown to be highly expressed in the substantia nigra of the brain, a region of neuronal degeneration in patients with Parkinson's disease ; however, no direct relation to Parkinson's disease has been established. Two transcript variants encoding the same protein have been found for this gene.[ 7]
Beta-synuclein is a synuclein protein found primarily in brain tissue and is seen mainly in presynaptic terminals. Beta-synuclein is predominantly expressed in the neocortex , hippocampus , striatum , thalamus , and cerebellum . It is not found in Lewy bodies , but it is associated with hippocampal pathology in PD and DLB .[ 8]
Beta-synuclein is suggested to be an inhibitor of alpha-synuclein aggregation, which occurs in neurodegenerative diseases such as Parkinson's disease . Thus, beta-synuclein may protect the central nervous system from the neurotoxic effects of alpha-synuclein and provide a novel treatment of neurodegenerative disorders.[ 9] [ 10]
See also
References
^ a b c GRCh38: Ensembl release 89: ENSG00000074317 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034891 – 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 .^ Spillantini MG, Divane A, Goedert M (Nov 1995). "Assignment of human alpha-synuclein (SNCA) and beta-synuclein (SNCB) genes to chromosomes 4q21 and 5q35". Genomics . 27 (2): 379–81. doi :10.1006/geno.1995.1063 . PMID 7558013 . ^ Lavedan C, Leroy E, Torres R, Dehejia A, Dutra A, Buchholtz S, Nussbaum RL, Polymeropoulos MH (Jan 1999). "Genomic organization and expression of the human beta-synuclein gene (SNCB)" . Genomics . 54 (1): 173–5. doi :10.1006/geno.1998.5556 PMID 9806846 . ^ a b "Entrez Gene: SNCB synuclein, beta" .^ George, JM (2002). "The synucleins" . Genome Biology . 3 (1): REVIEWS3002. doi :10.1186/gb-2001-3-1-reviews3002 PMC 150459 PMID 11806835 . ^ Hashimoto, M; Bar-On, P; Ho, G; Takenouchi, T; Rockenstein, E; Crews, L; Masliah, E (2004). "Beta-synuclein regulates Akt activity in neuronal cells. A possible mechanism for neuroprotection in Parkinson's disease" . The Journal of Biological Chemistry . 279 (22): 23622–9. doi :10.1074/jbc.M313784200 PMID 15026413 . ^ Hashimoto, M; Rockenstein, E; Mante, M; Mallory, M; Masliah, E (2001). "beta-Synuclein inhibits alpha-synuclein aggregation: a possible role as an anti-parkinsonian factor" . Neuron . 32 (2): 213–23. doi :10.1016/S0896-6273(01)00462-7 PMID 11683992 . S2CID 14766899 .
Further reading
Jakes R, Spillantini MG, Goedert M (1994). "Identification of two distinct synucleins from human brain" . FEBS Lett . 345 (1): 27–32. doi :10.1016/0014-5793(94)00395-5 PMID 8194594 . S2CID 36840279 . Jensen PH, Hojrup P, Hager H, et al. (1997). "Binding of Abeta to alpha- and beta-synucleins: identification of segments in alpha-synuclein/NAC precursor that bind Abeta and NAC" . Biochem. J . 323 (Pt 2): 539–46. doi :10.1042/bj3230539 . PMC 1218353 PMID 9163350 . Pronin AN, Morris AJ, Surguchov A, Benovic JL (2000). "Synucleins are a novel class of substrates for G protein-coupled receptor kinases" . J. Biol. Chem . 275 (34): 26515–22. doi :10.1074/jbc.M003542200 PMID 10852916 . Rockenstein E, Hansen LA, Mallory M, et al. (2001). "Altered expression of the synuclein family mRNA in Lewy body and Alzheimer's disease". Brain Res . 914 (1–2): 48–56. doi :10.1016/S0006-8993(01)02772-X . PMID 11578596 . S2CID 35448948 . Tanji K, Mori F, Nakajo S, et al. (2001). "Expression of beta-synuclein in normal human astrocytes". NeuroReport . 12 (13): 2845–8. doi :10.1097/00001756-200109170-00018 . PMID 11588588 . S2CID 84671534 . Hashimoto M, Rockenstein E, Mante M, et al. (2001). "beta-Synuclein inhibits alpha-synuclein aggregation: a possible role as an anti-parkinsonian factor" . Neuron . 32 (2): 213–23. doi :10.1016/S0896-6273(01)00462-7 PMID 11683992 . S2CID 14766899 . Uversky VN, Li J, Souillac P, et al. (2002). "Biophysical properties of the synucleins and their propensities to fibrillate: inhibition of alpha-synuclein assembly by beta- and gamma-synucleins" . J. Biol. Chem . 277 (14): 11970–8. doi :10.1074/jbc.M109541200 PMID 11812782 . Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences" . Proc. Natl. Acad. Sci. U.S.A . 99 (26): 16899–903. Bibcode :2002PNAS...9916899M . doi :10.1073/pnas.242603899 PMC 139241 PMID 12477932 . Ihara M, Tomimoto H, Kitayama H, et al. (2003). "Association of the cytoskeletal GTP-binding protein Sept4/H5 with cytoplasmic inclusions found in Parkinson's disease and other synucleinopathies" . J. Biol. Chem . 278 (26): 24095–102. doi :10.1074/jbc.M301352200 PMID 12695511 . Fung KM, Rorke LB, Giasson B, et al. (2003). "Expression of alpha-, beta-, and gamma-synuclein in glial tumors and medulloblastomas". Acta Neuropathol . 106 (2): 167–75. doi :10.1007/s00401-003-0718-x . PMID 12783249 . S2CID 39712533 . da Costa CA, Masliah E, Checler F (2003). "Beta-synuclein displays an antiapoptotic p53-dependent phenotype and protects neurons from 6-hydroxydopamine-induced caspase 3 activation: cross-talk with alpha-synuclein and implication for Parkinson's disease" . J. Biol. Chem . 278 (39): 37330–5. doi :10.1074/jbc.M306083200 PMID 12867415 . Ohtake H, Limprasert P, Fan Y, et al. (2005). "β-Synuclein gene alterations in dementia with Lewy bodies" . Neurology . 63 (5): 805–11. doi :10.1212/01.wnl.0000139870.14385.3c . PMC 1808539 PMID 15365127 . Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)" . Genome Res . 14 (10B): 2121–7. doi :10.1101/gr.2596504 . PMC 528928 PMID 15489334 . Snyder H, Mensah K, Hsu C, et al. (2005). "beta-Synuclein reduces proteasomal inhibition by alpha-synuclein but not gamma-synuclein" . J. Biol. Chem . 280 (9): 7562–9. doi :10.1074/jbc.M412887200 PMID 15591046 . Sung YH, Eliezer D (2006). "Secondary structure and dynamics of micelle bound β- and γ-synuclein" . Protein Sci . 15 (5): 1162–74. doi :10.1110/ps.051803606 . PMC 2242515 PMID 16597821 . Fan Y, Limprasert P, Murray IV, et al. (2006). "Beta-synuclein modulates alpha-synuclein neurotoxicity by reducing alpha-synuclein protein expression" . Hum. Mol. Genet . 15 (20): 3002–11. doi :10.1093/hmg/ddl242 PMID 16959793 . Myslinski E, Gérard MA, Krol A, Carbon P (2007). "A genome scale location analysis of human Staf/ZNF143-binding sites suggests a widespread role for human Staf/ZNF143 in mammalian promoters" . J. Biol. Chem . 281 (52): 39953–62. doi :10.1074/jbc.M608507200 PMID 17092945 . Sung YH, Eliezer D (2007). "Residual structure, backbone dynamics, and interactions within the synuclein family" . J. Mol. Biol . 372 (3): 689–707. doi :10.1016/j.jmb.2007.07.008 . PMC 2094134 PMID 17681534 .
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