Overview:

Alpha-Synuclein (SNCA) is expressed predominantly in the brain, where it is concentrated in presynaptic nerve terminals (1). Alpha-synuclein is highly expressed in the mitochondria of the olfactory bulb, hippocampus, striatum and thalamus (2). Functionally, it has been shown to significantly interact with tubulin (3), and may serve as a potential microtubule-associated protein. It has also been found to be essential for normal development of the cognitive functions; inactivation may lead to impaired spatial learning and working memory (4). SNCA fibrillar aggregates represent the major non A-beta component of Alzheimers disease amyloid plaque, and a major component of Lewy body inclusions, and Parkinson's disease. Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive accumulation in selected neurons of protein inclusions containing alpha-synuclein and ubiquitin (5, 6). Alpha synuclein phosphorylated at serine 129 constitutes 90% of the alpha synuclein found in Lewy bodies (7, 8).

References:

1. “Genetics Home Reference: SNCA”. US National Library of Medicine. (2013).
2. Zhang L., et al. (2008) Brain Res. 1244: 40-52.
3. Alim M.A., et al. (2002) J Biol Chem. 277(3): 2112-2117.
4. Kokhan V.S., Afanasyeva M.A., Van'kin G. (2012) Behav. Brain. Res. 231(1): 226-230.
5. Spillantini M.G., et al. (1997) Nature. 388(6645): 839-840.
6. Mezey E., et al. (1998) Nat Med. 4(7): 755-757.
7. Fujiwara H., et al. (2002) Nat Cell Biol. 4(2):160-4.
8. Anderson J.P., et al. (2006) J Biol Chem. 281(40):29739-52.