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Gene Review

SNCA  -  synuclein, alpha (non A4 component of...

Homo sapiens

Synonyms: Alpha-synuclein, NACP, Non-A beta component of AD amyloid, Non-A4 component of amyloid precursor, PARK1, ...
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Disease relevance of SNCA


Psychiatry related information on SNCA


High impact information on SNCA


Chemical compound and disease context of SNCA


Biological context of SNCA

  • Alleles at NACP-Rep1, the polymorphic microsatellite repeat located approximately 10 kb upstream of the alpha -synuclein gene (SNCA), are associated, in some reports, with differing risks of sporadic Parkinson disease (PD) [1].
  • Furthermore, PARP-1 binding to NACP-Rep1 specifically reduced the transcriptional activity of the SNCA promoter/enhancer in luciferase reporter assays [1].
  • Inhibition of PARP-1's catalytic domain increased the endogenous SNCA mRNA levels in cultured SH-SY5Y cells [1].
  • Because there was exactly the same difference between the regions originated from each patient, the finding suggests that the phenotype of SNCA multiplication may be also influenced by the range of duplication region [2].
  • There was an increased risk of PD for persons with either SNCA 261/261 or MAPT H1/H1 genotypes as compared with persons with neither (odds ratio, 1.96; 95% confidence interval, 1.34-2.86; p = 0.0003) [21].

Anatomical context of SNCA


Associations of SNCA with chemical compounds


Physical interactions of SNCA


Enzymatic interactions of SNCA


Co-localisations of SNCA


Regulatory relationships of SNCA


Other interactions of SNCA


Analytical, diagnostic and therapeutic context of SNCA


  1. Regulation of alpha-synuclein expression by poly (ADP ribose) polymerase-1 (PARP-1) binding to the NACP-Rep1 polymorphic site upstream of the SNCA gene. Chiba-Falek, O., Kowalak, J.A., Smulson, M.E., Nussbaum, R.L. Am. J. Hum. Genet. (2005) [Pubmed]
  2. Clinical heterogeneity of alpha-synuclein gene duplication in Parkinson's disease. Nishioka, K., Hayashi, S., Farrer, M.J., Singleton, A.B., Yoshino, H., Imai, H., Kitami, T., Sato, K., Kuroda, R., Tomiyama, H., Mizoguchi, K., Murata, M., Toda, T., Imoto, I., Inazawa, J., Mizuno, Y., Hattori, N. Ann. Neurol. (2006) [Pubmed]
  3. SNCA multiplication is not a common cause of Parkinson disease or dementia with Lewy bodies. Johnson, J., Hague, S.M., Hanson, M., Gibson, A., Wilson, K.E., Evans, E.W., Singleton, A.A., McInerney-Leo, A., Nussbaum, R.L., Hernandez, D.G., Gallardo, M., McKeith, I.G., Burn, D.J., Ryu, M., Hellstrom, O., Ravina, B., Eerola, J., Perry, R.H., Jaros, E., Tienari, P., Weiser, R., Gwinn-Hardy, K., Morris, C.M., Hardy, J., Singleton, A.B. Neurology (2004) [Pubmed]
  4. Parkin: a multipurpose neuroprotective agent? Feany, M.B., Pallanck, L.J. Neuron (2003) [Pubmed]
  5. Phosphorylated protein kinases associated with neuronal and glial tau deposits in argyrophilic grain disease. Ferrer, I., Barrachina, M., Tolnay, M., Rey, M.J., Vidal, N., Carmona, M., Blanco, R., Puig, B. Brain Pathol. (2003) [Pubmed]
  6. Quantitative proteomics identifies surfactant-resistant alpha-synuclein in cerebral cortex of Parkinsonism-dementia complex of Guam but not Alzheimer's disease or progressive supranuclear palsy. Yang, W., Woltjer, R.L., Sokal, I., Pan, C., Wang, Y., Brodey, M., Peskind, E.R., Leverenz, J.B., Zhang, J., Perl, D.P., Galasko, D.R., Montine, T.J. Am. J. Pathol. (2007) [Pubmed]
  7. Human and mouse alpha-synuclein genes: comparative genomic sequence analysis and identification of a novel gene regulatory element. Touchman, J.W., Dehejia, A., Chiba-Falek, O., Cabin, D.E., Schwartz, J.R., Orrison, B.M., Polymeropoulos, M.H., Nussbaum, R.L. Genome Res. (2001) [Pubmed]
  8. Association of Alcohol Craving With alpha-Synuclein (SNCA). Foroud, T., Wetherill, L.F., Liang, T., Dick, D.M., Hesselbrock, V., Kramer, J., Nurnberger, J., Schuckit, M., Carr, L., Porjesz, B., Xuei, X., Edenberg, H.J. Alcohol. Clin. Exp. Res. (2007) [Pubmed]
  9. Linkage Disequilibrium and Association Analysis of alpha-Synuclein and Alcohol and Drug Dependence in Two American Indian Populations. Clarimon, J., Gray, R.R., Williams, L.N., Enoch, M.A., Robin, R.W., Albaugh, B., Singleton, A., Goldman, D., Mulligan, C.J. Alcohol. Clin. Exp. Res. (2007) [Pubmed]
  10. Locomotor activity and evoked dopamine release are reduced in mice overexpressing A30P-mutated human alpha-synuclein. Yavich, L., Oksman, M., Tanila, H., Kerokoski, P., Hiltunen, M., van Groen, T., Puoliväli, J., Männistö, P.T., García-Horsman, A., MacDonald, E., Beyreuther, K., Hartmann, T., Jäkälä, P. Neurobiol. Dis. (2005) [Pubmed]
  11. Tau and alpha-synuclein in susceptibility to, and dementia in, Parkinson's disease. Goris, A., Williams-Gray, C.H., Clark, G.R., Foltynie, T., Lewis, S.J., Brown, J., Ban, M., Spillantini, M.G., Compston, A., Burn, D.J., Chinnery, P.F., Barker, R.A., Sawcer, S.J. Ann. Neurol. (2007) [Pubmed]
  12. The biochemistry of Parkinson's disease. Cookson, M.R. Annu. Rev. Biochem. (2005) [Pubmed]
  13. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Chandra, S., Gallardo, G., Fernández-Chacón, R., Schlüter, O.M., Südhof, T.C. Cell (2005) [Pubmed]
  14. The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility. Liu, Y., Fallon, L., Lashuel, H.A., Liu, Z., Lansbury, P.T. Cell (2002) [Pubmed]
  15. Synphilin-1 associates with alpha-synuclein and promotes the formation of cytosolic inclusions. Engelender, S., Kaminsky, Z., Guo, X., Sharp, A.H., Amaravi, R.K., Kleiderlein, J.J., Margolis, R.L., Troncoso, J.C., Lanahan, A.A., Worley, P.F., Dawson, V.L., Dawson, T.M., Ross, C.A. Nat. Genet. (1999) [Pubmed]
  16. Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Chung, K.K., Zhang, Y., Lim, K.L., Tanaka, Y., Huang, H., Gao, J., Ross, C.A., Dawson, V.L., Dawson, T.M. Nat. Med. (2001) [Pubmed]
  17. 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. da Costa, C.A., Masliah, E., Checler, F. J. Biol. Chem. (2003) [Pubmed]
  18. Age-associated increases of alpha-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: Is this the target for Parkinson's disease? Chu, Y., Kordower, J.H. Neurobiol. Dis. (2007) [Pubmed]
  19. Gamma synuclein: subcellular localization in neuronal and non-neuronal cells and effect on signal transduction. Surguchov, A., Palazzo, R.E., Surgucheva, I. Cell Motil. Cytoskeleton (2001) [Pubmed]
  20. MPP+ increases alpha-synuclein expression and ERK/MAP-kinase phosphorylation in human neuroblastoma SH-SY5Y cells. Gómez-Santos, C., Ferrer, I., Reiriz, J., Viñals, F., Barrachina, M., Ambrosio, S. Brain Res. (2002) [Pubmed]
  21. Interaction of alpha-synuclein and tau genotypes in Parkinson's disease. Mamah, C.E., Lesnick, T.G., Lincoln, S.J., Strain, K.J., de Andrade, M., Bower, J.H., Ahlskog, J.E., Rocca, W.A., Farrer, M.J., Maraganore, D.M. Ann. Neurol. (2005) [Pubmed]
  22. Functional analysis of intra-allelic variation at NACP-Rep1 in the alpha-synuclein gene. Chiba-Falek, O., Touchman, J.W., Nussbaum, R.L. Hum. Genet. (2003) [Pubmed]
  23. Unaltered alpha-synuclein blood levels in juvenile Parkinsonism with a parkin exon 4 deletion. Miller, D.W., Crawley, A., Gwinn-Hardy, K., Lopez, G., Nussbaum, R., Cookson, M.R., Singleton, A.B., Hardy, J., Dogu, O. Neurosci. Lett. (2005) [Pubmed]
  24. Early-onset dementia with Lewy bodies. Takao, M., Ghetti, B., Yoshida, H., Piccardo, P., Narain, Y., Murrell, J.R., Vidal, R., Glazier, B.S., Jakes, R., Tsutsui, M., Spillantini, M.G., Crowther, R.A., Goedert, M., Koto, A. Brain Pathol. (2004) [Pubmed]
  25. Casein kinase II-mediated phosphorylation regulates alpha-synuclein/synphilin-1 interaction and inclusion body formation. Lee, G., Tanaka, M., Park, K., Lee, S.S., Kim, Y.M., Junn, E., Lee, S.H., Mouradian, M.M. J. Biol. Chem. (2004) [Pubmed]
  26. Synphilin-1 is developmentally localized to synaptic terminals, and its association with synaptic vesicles is modulated by alpha-synuclein. Ribeiro, C.S., Carneiro, K., Ross, C.A., Menezes, J.R., Engelender, S. J. Biol. Chem. (2002) [Pubmed]
  27. Genetics of Parkinsonism: a review. Vaughan, J.R., Davis, M.B., Wood, N.W. Ann. Hum. Genet. (2001) [Pubmed]
  28. Alpha-synuclein and parkin contribute to the assembly of ubiquitin lysine 63-linked multiubiquitin chains. Doss-Pepe, E.W., Chen, L., Madura, K. J. Biol. Chem. (2005) [Pubmed]
  29. Parkin accumulation in aggresomes due to proteasome impairment. Junn, E., Lee, S.S., Suhr, U.T., Mouradian, M.M. J. Biol. Chem. (2002) [Pubmed]
  30. Single particle characterization of iron-induced pore-forming alpha-synuclein oligomers. Kostka, M., Högen, T., Danzer, K.M., Levin, J., Habeck, M., Wirth, A., Wagner, R., Glabe, C.G., Finger, S., Heinzelmann, U., Garidel, P., Duan, W., Ross, C.A., Kretzschmar, H., Giese, A. J. Biol. Chem. (2008) [Pubmed]
  31. Microtubule-associated protein 1B is a component of cortical Lewy bodies and binds alpha-synuclein filaments. Jensen, P.H., Islam, K., Kenney, J., Nielsen, M.S., Power, J., Gai, W.P. J. Biol. Chem. (2000) [Pubmed]
  32. alpha-Synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells. Ahn, B.H., Rhim, H., Kim, S.Y., Sung, Y.M., Lee, M.Y., Choi, J.Y., Wolozin, B., Chang, J.S., Lee, Y.H., Kwon, T.K., Chung, K.C., Yoon, S.H., Hahn, S.J., Kim, M.S., Jo, Y.H., Min, d.o. .S. J. Biol. Chem. (2002) [Pubmed]
  33. Synphilin-1 degradation by the ubiquitin-proteasome pathway and effects on cell survival. Lee, G., Junn, E., Tanaka, M., Kim, Y.M., Mouradian, M.M. J. Neurochem. (2002) [Pubmed]
  34. Binding of Abeta to alpha- and beta-synucleins: identification of segments in alpha-synuclein/NAC precursor that bind Abeta and NAC. Jensen, P.H., Hojrup, P., Hager, H., Nielsen, M.S., Jacobsen, L., Olesen, O.F., Gliemann, J., Jakes, R. Biochem. J. (1997) [Pubmed]
  35. Agrin binds alpha-synuclein and modulates alpha-synuclein fibrillation. Liu, I.H., Uversky, V.N., Munishkina, L.A., Fink, A.L., Halfter, W., Cole, G.J. Glycobiology (2005) [Pubmed]
  36. Monoubiquitylation of alpha-synuclein by seven in absentia homolog (SIAH) promotes its aggregation in dopaminergic cells. Rott, R., Szargel, R., Haskin, J., Shani, V., Shainskaya, A., Manov, I., Liani, E., Avraham, E., Engelender, S. J. Biol. Chem. (2008) [Pubmed]
  37. Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease. Shimura, H., Schlossmacher, M.G., Hattori, N., Frosch, M.P., Trockenbacher, A., Schneider, R., Mizuno, Y., Kosik, K.S., Selkoe, D.J. Science (2001) [Pubmed]
  38. The oxidation state of DJ-1 regulates its chaperone activity toward alpha-synuclein. Zhou, W., Zhu, M., Wilson, M.A., Petsko, G.A., Fink, A.L. J. Mol. Biol. (2006) [Pubmed]
  39. The role of G-protein-coupled receptor kinase 5 in pathogenesis of sporadic Parkinson's disease. Arawaka, S., Wada, M., Goto, S., Karube, H., Sakamoto, M., Ren, C.H., Koyama, S., Nagasawa, H., Kimura, H., Kawanami, T., Kurita, K., Tajima, K., Daimon, M., Baba, M., Kido, T., Saino, S., Goto, K., Asao, H., Kitanaka, C., Takashita, E., Hongo, S., Nakamura, T., Kayama, T., Suzuki, Y., Kobayashi, K., Katagiri, T., Kurokawa, K., Kurimura, M., Toyoshima, I., Niizato, K., Tsuchiya, K., Iwatsubo, T., Muramatsu, M., Matsumine, H., Kato, T. J. Neurosci. (2006) [Pubmed]
  40. Tissue transglutaminase catalyzes the formation of alpha-synuclein crosslinks in Parkinson's disease. Andringa, G., Lam, K.Y., Chegary, M., Wang, X., Chase, T.N., Bennett, M.C. FASEB J. (2004) [Pubmed]
  41. Aggresomes formed by alpha-synuclein and synphilin-1 are cytoprotective. Tanaka, M., Kim, Y.M., Lee, G., Junn, E., Iwatsubo, T., Mouradian, M.M. J. Biol. Chem. (2004) [Pubmed]
  42. Quantitative proteomic analysis of mitochondrial proteins: relevance to Lewy body formation and Parkinson's disease. Jin, J., Meredith, G.E., Chen, L., Zhou, Y., Xu, J., Shie, F.S., Lockhart, P., Zhang, J. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  43. Modulation of dopamine transporter function by alpha-synuclein is altered by impairment of cell adhesion and by induction of oxidative stress. Wersinger, C., Prou, D., Vernier, P., Sidhu, A. FASEB J. (2003) [Pubmed]
  44. beta-Synuclein inhibits alpha-synuclein aggregation: a possible role as an anti-parkinsonian factor. Hashimoto, M., Rockenstein, E., Mante, M., Mallory, M., Masliah, E. Neuron (2001) [Pubmed]
  45. Alpha-synuclein and its disease-causing mutants induce ICAM-1 and IL-6 in human astrocytes and astrocytoma cells. Klegeris, A., Giasson, B.I., Zhang, H., Maguire, J., Pelech, S., McGeer, P.L. FASEB J. (2006) [Pubmed]
  46. Alpha-synuclein expression is up-regulated in NTera2 cells during neuronal differentiation but unaffected by exposure to cytokines and neurotrophic factors. Satoh, J.I., Kuroda, Y. Parkinsonism Relat. Disord. (2001) [Pubmed]
  47. Role of cytochrome c as a stimulator of alpha-synuclein aggregation in Lewy body disease. Hashimoto, M., Takeda, A., Hsu, L.J., Takenouchi, T., Masliah, E. J. Biol. Chem. (1999) [Pubmed]
  48. Alpha-synuclein controls mitochondrial calcium homeostasis by enhancing endoplasmic reticulum-mitochondria interactions. Cali', T., Ottolini, D., Negro, A., Brini, M. J. Biol. Chem. (2012) [Pubmed]
  49. beta-Synuclein reduces proteasomal inhibition by alpha-synuclein but not gamma-synuclein. Snyder, H., Mensah, K., Hsu, C., Hashimoto, M., Surgucheva, I.G., Festoff, B., Surguchov, A., Masliah, E., Matouschek, A., Wolozin, B. J. Biol. Chem. (2005) [Pubmed]
  50. Effect of allelic variation at the NACP-Rep1 repeat upstream of the alpha-synuclein gene (SNCA) on transcription in a cell culture luciferase reporter system. Chiba-Falek, O., Nussbaum, R.L. Hum. Mol. Genet. (2001) [Pubmed]
  51. The co-chaperone carboxyl terminus of Hsp70-interacting protein (CHIP) mediates alpha-synuclein degradation decisions between proteasomal and lysosomal pathways. Shin, Y., Klucken, J., Patterson, C., Hyman, B.T., McLean, P.J. J. Biol. Chem. (2005) [Pubmed]
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