Alpha-synuclein Modulates Dopamine Neurotransmission

Overview

Journal J Chem Neuroanat

Specialties Anatomy & Histology
Chemistry
Neurology

Date 2016 Jun 24

PMID 27334403

Citations 25

Authors

Brittany Butler

Danielle Sambo

Habibeh Khoshbouei

Affiliations

Soon will be listed here.

Abstract

Alpha-synuclein is a small, highly charged protein encoded by the synuclein or SNCA gene that is predominantly expressed in central nervous system neurons. Although its physiological function remains enigmatic, alpha-synuclein is implicated in movement disorders such as Parkinson's disease, multiple system atrophy, and in neurodegenerative diseases such as Dementia with Lewy bodies. Here we have focused on reviewing the existing literature pertaining to wild-type alpha-synuclein structure, its properties, and its potential involvement in regulation of dopamine neurotransmission.

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References

Peng X, Peng X, Tehranian R, Dietrich P, Stefanis L, Perez R . Alpha-synuclein activation of protein phosphatase 2A reduces tyrosine hydroxylase phosphorylation in dopaminergic cells. J Cell Sci. 2005; 118(Pt 15):3523-30. DOI: 10.1242/jcs.02481. View

Ostrerova N, Petrucelli L, Farrer M, Mehta N, Choi P, Hardy J . alpha-Synuclein shares physical and functional homology with 14-3-3 proteins. J Neurosci. 1999; 19(14):5782-91. PMC: 6783081. View

Ueda K, Fukushima H, Masliah E, Xia Y, Iwai A, Yoshimoto M . Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proc Natl Acad Sci U S A. 1993; 90(23):11282-6. PMC: 47966. DOI: 10.1073/pnas.90.23.11282. View

Jakes R, Spillantini M, Goedert M . Identification of two distinct synucleins from human brain. FEBS Lett. 1994; 345(1):27-32. DOI: 10.1016/0014-5793(94)00395-5. View

Anderson J, Walker D, Goldstein J, de Laat R, Banducci K, Caccavello R . Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J Biol Chem. 2006; 281(40):29739-52. DOI: 10.1074/jbc.M600933200. View

Pena-Oliver Y, Buchman V, Dalley J, Robbins T, Schumann G, Ripley T . Deletion of alpha-synuclein decreases impulsivity in mice. Genes Brain Behav. 2011; 11(2):137-46. PMC: 3380554. DOI: 10.1111/j.1601-183X.2011.00758.x. View

Burre J, Sharma M, Tsetsenis T, Buchman V, Etherton M, Sudhof T . Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science. 2010; 329(5999):1663-7. PMC: 3235365. DOI: 10.1126/science.1195227. View

Ronzitti G, Bucci G, Emanuele M, Leo D, Sotnikova T, Mus L . Exogenous α-synuclein decreases raft partitioning of Cav2.2 channels inducing dopamine release. J Neurosci. 2014; 34(32):10603-15. PMC: 6802592. DOI: 10.1523/JNEUROSCI.0608-14.2014. View

Garcia-Reitboeck P, Anichtchik O, Dalley J, Ninkina N, Tofaris G, Buchman V . Endogenous alpha-synuclein influences the number of dopaminergic neurons in mouse substantia nigra. Exp Neurol. 2013; 248:541-5. PMC: 4104299. DOI: 10.1016/j.expneurol.2013.07.015. View

10.

Lee F, Liu F, Pristupa Z, Niznik H . Direct binding and functional coupling of alpha-synuclein to the dopamine transporters accelerate dopamine-induced apoptosis. FASEB J. 2001; 15(6):916-26. DOI: 10.1096/fj.00-0334com. View

11.

Kahle P, Neumann M, Ozmen L, Muller V, Jacobsen H, Schindzielorz A . Subcellular localization of wild-type and Parkinson's disease-associated mutant alpha -synuclein in human and transgenic mouse brain. J Neurosci. 2000; 20(17):6365-73. PMC: 6772969. View

12.

Liu Y, Schweitzer E, Nirenberg M, Pickel V, Evans C, EDWARDS R . Preferential localization of a vesicular monoamine transporter to dense core vesicles in PC12 cells. J Cell Biol. 1994; 127(5):1419-33. PMC: 2120259. DOI: 10.1083/jcb.127.5.1419. View

13.

Wersinger C, Sidhu A . Differential cytotoxicity of dopamine and H2O2 in a human neuroblastoma divided cell line transfected with alpha-synuclein and its familial Parkinson's disease-linked mutants. Neurosci Lett. 2003; 342(1-2):124-8. DOI: 10.1016/s0304-3940(03)00212-x. View

14.

Gaugler M, Genc O, Bobela W, Mohanna S, Ardah M, El-Agnaf O . Nigrostriatal overabundance of α-synuclein leads to decreased vesicle density and deficits in dopamine release that correlate with reduced motor activity. Acta Neuropathol. 2012; 123(5):653-69. DOI: 10.1007/s00401-012-0963-y. View

15.

Bennett M . Molecular mechanisms of neurotransmitter release. Ann N Y Acad Sci. 1994; 733:256-65. DOI: 10.1111/j.1749-6632.1994.tb17275.x. View

16.

Pimoule C, Schoemaker H, Scatton B, Agid Y, Langer S . Decrease in [3H]cocaine binding to the dopamine transporter in Parkinson's disease. Eur J Pharmacol. 1983; 95(1-2):145-6. DOI: 10.1016/0014-2999(83)90281-9. View

17.

Abeliovich A, Schmitz Y, Farinas I, Choi-Lundberg D, Ho W, Castillo P . Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron. 2000; 25(1):239-52. DOI: 10.1016/s0896-6273(00)80886-7. View

18.

Ben Gedalya T, Loeb V, Israeli E, Altschuler Y, Selkoe D, Sharon R . Alpha-synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling. Traffic. 2008; 10(2):218-34. PMC: 2694501. DOI: 10.1111/j.1600-0854.2008.00853.x. View

19.

Clayton D, George J . The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease. Trends Neurosci. 1998; 21(6):249-54. DOI: 10.1016/s0166-2236(97)01213-7. View

20.

Jones S, Gainetdinov R, Hu X, Cooper D, Wightman R, White F . Loss of autoreceptor functions in mice lacking the dopamine transporter. Nat Neurosci. 1999; 2(7):649-55. DOI: 10.1038/10204. View