Note: This antibody will also bind human alpha-synuclein containing the A30P and A53T mutations.
Alpha synuclein is a member of the synuclein family, the other two proteins being beta and gamma synuclein. Alpha synuclein was originally isolated as a major synaptic vesicle associated protein from the electric organ of the fish Torpedo (1). Direct homologues of alpha-synuclein are found in all vertebrates. Later work connected alpha-synuclein with human brain pathology, when a protein originally identified as a component of NAC, the "Non-Amyloid beta Component of Alzheimer's disease amyloid" proved to be a peptide derived from alpha-synuclein (2).
The alpha-synuclein protein is therefore sometimes known as NAC precursor or NACP. Further work showed that alpha-synuclein is a major component of the Lewy bodies of Parkinson's disease and point mutations of alpha-synuclein proved to be causative of some forms of familial Parkinson's disease (3, 4, 5). However, despite being discovered as component of amyloid preparations, alpha-synuclein is apparently not a major component of the senile plaques of Alzheimer's disease (6). Early onset Parkinson's disease may be caused by a duplication or triplication of one of the alpha synuclein genes (7, 8). Alpha-synuclein is also found in the Lewy bodies of patients with diffuse Lewy body disease and inclusions in glial cells in the brains of patients with multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS). Alpha-synuclein is heavily expressed in brain and appears to be localized primarily to presynaptic regions, though not with a typical synaptic vesicle distribution pattern. The synuclein proteins appear to have little 3D structure in solution, and probably belong to the family of "intrinsically unstructured proteins" which only adopt a well-defined conformation when bound to other proteins or membrane lipids (9). An excellent recent review of the role of alpha-synuclein in health and disease was recently published by Mark Cookson (10).
1. Maroteaux, L., J.T. Campanelli, and R.H. Scheller. Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J. Neurosci. 8:2804-2815 (1988).
2. Lavedan, C. The Synuclein Family. Genome Research 8:871-880 (1998).
3. Polymeropoulos, MH et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276: 2045-2047 (1997).
4. Kruger, R et al. Ala30-to-Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nature Genet. 18: 106-108 (1998).
5. Chartier-Harlin, M-C. et al. Alpha-synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 364: 1167-1169 (2004).
6. Singleton, AB.et al. Alpha-synuclein locus triplication causes Parkinson's disease. Science 302: 841 (2003).
7. Culvenor, J.G. et al. Non-Abeta component of Alzheimer's disease amyloid (NAC) revisited: NAC and alpha-synuclein are not associated with Abeta amyloid. Am. J. Pathol. 155:1173-1181 (1999).
8. Ibanez, P. et al. Causal relation between alpha-synuclein gene duplication and familial Parkinson's disease. Lancet 364:1169-1171 (2004).
9. Dyson, HJ. and Wright, PE. Intrinsically unstructured proteins and their functions. Nature Reviews of Molecular and Cellular Biology 6:197-208 (2005).
10. Cookson MR. Alpha-Synuclein and neuronal cell death. Mol Neurodeg 4:9 (2009).
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