Beta-synuclein explained

Beta-synuclein is a protein that in humans is encoded by the SNCB gene.^{[1] [2] [3]}

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.^[3]

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.^[4]

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.^{[5] [6]}

See also

• Synuclein

Further reading

• Jakes R, Spillantini MG, Goedert M . Identification of two distinct synucleins from human brain . FEBS Lett. . 345 . 1 . 27–32 . 1994 . 8194594 . 10.1016/0014-5793(94)00395-5 . 36840279 . free .
• Jensen PH, Hojrup P, Hager H . 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 . 1997 . 9163350 . 10.1042/bj3230539. 1218353 . etal.
• Pronin AN, Morris AJ, Surguchov A, Benovic JL . Synucleins are a novel class of substrates for G protein-coupled receptor kinases . J. Biol. Chem. . 275 . 34 . 26515–22 . 2000 . 10852916 . 10.1074/jbc.M003542200 . free .
• Rockenstein E, Hansen LA, Mallory M . Altered expression of the synuclein family mRNA in Lewy body and Alzheimer's disease . Brain Res. . 914 . 1–2 . 48–56 . 2001 . 11578596 . 10.1016/S0006-8993(01)02772-X . 35448948 . etal.
• Tanji K, Mori F, Nakajo S . Expression of beta-synuclein in normal human astrocytes . NeuroReport . 12 . 13 . 2845–8 . 2001 . 11588588 . 10.1097/00001756-200109170-00018 . 84671534 . etal.
• Hashimoto M, Rockenstein E, Mante M . beta-Synuclein inhibits alpha-synuclein aggregation: a possible role as an anti-parkinsonian factor . Neuron . 32 . 2 . 213–23 . 2001 . 11683992 . 10.1016/S0896-6273(01)00462-7 . 14766899 . etal. free .
• Uversky VN, Li J, Souillac P . 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 . 2002 . 11812782 . 10.1074/jbc.M109541200 . etal. free .
• Strausberg RL, Feingold EA, Grouse LH . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Ihara M, Tomimoto H, Kitayama H . 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 . 2003 . 12695511 . 10.1074/jbc.M301352200 . etal. free .
• Fung KM, Rorke LB, Giasson B . Expression of alpha-, beta-, and gamma-synuclein in glial tumors and medulloblastomas . Acta Neuropathol. . 106 . 2 . 167–75 . 2003 . 12783249 . 10.1007/s00401-003-0718-x . 39712533 . etal.
• da Costa CA, Masliah E, Checler F . 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 . 2003 . 12867415 . 10.1074/jbc.M306083200 . free .
• Ohtake H, Limprasert P, Fan Y . β-Synuclein gene alterations in dementia with Lewy bodies . Neurology . 63 . 5 . 805–11 . 2005 . 15365127 . 10.1212/01.wnl.0000139870.14385.3c. 1808539 . etal.
• Gerhard DS, Wagner L, Feingold EA . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Snyder H, Mensah K, Hsu C . beta-Synuclein reduces proteasomal inhibition by alpha-synuclein but not gamma-synuclein . J. Biol. Chem. . 280 . 9 . 7562–9 . 2005 . 15591046 . 10.1074/jbc.M412887200 . etal. free .
• Sung YH, Eliezer D . Secondary structure and dynamics of micelle bound β- and γ-synuclein . Protein Sci. . 15 . 5 . 1162–74 . 2006 . 16597821 . 10.1110/ps.051803606 . 2242515 .
• Fan Y, Limprasert P, Murray IV . Beta-synuclein modulates alpha-synuclein neurotoxicity by reducing alpha-synuclein protein expression . Hum. Mol. Genet. . 15 . 20 . 3002–11 . 2006 . 16959793 . 10.1093/hmg/ddl242 . etal. free .
• Myslinski E, Gérard MA, Krol A, Carbon P . 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 . 2007 . 17092945 . 10.1074/jbc.M608507200 . free .
• Sung YH, Eliezer D . Residual structure, backbone dynamics, and interactions within the synuclein family . J. Mol. Biol. . 372 . 3 . 689–707 . 2007 . 17681534 . 10.1016/j.jmb.2007.07.008 . 2094134 .

Notes and References

1. Spillantini MG, Divane A, Goedert M . Assignment of human alpha-synuclein (SNCA) and beta-synuclein (SNCB) genes to chromosomes 4q21 and 5q35 . Genomics . 27 . 2 . 379–81 . Nov 1995 . 7558013 . 10.1006/geno.1995.1063 .
2. Lavedan C, Leroy E, Torres R, Dehejia A, Dutra A, Buchholtz S, Nussbaum RL, Polymeropoulos MH . Genomic organization and expression of the human beta-synuclein gene (SNCB) . Genomics . 54 . 1 . 173–5 . Jan 1999 . 9806846 . 10.1006/geno.1998.5556 . free .
3. Web site: Entrez Gene: SNCB synuclein, beta.
4. George . JM . The synucleins . Genome Biology . 3 . 1 . REVIEWS3002 . 2002 . 11806835 . 150459 . 10.1186/gb-2001-3-1-reviews3002 . free .
5. Hashimoto . M . Bar-On . P . Ho . G . Takenouchi . T . Rockenstein . E . Crews . L . Masliah . E . 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 . 2004 . 15026413 . 10.1074/jbc.M313784200 . free .
6. Hashimoto . M . Rockenstein . E . Mante . M . Mallory . M . Masliah . E . beta-Synuclein inhibits alpha-synuclein aggregation: a possible role as an anti-parkinsonian factor . Neuron . 32 . 2 . 213–23 . 2001 . 11683992 . 10.1016/S0896-6273(01)00462-7. 14766899 . free .