Overview:

Alpha-synuclein is expressed in the presynaptic terminal of the neuron where it is implicated in the formation of SNARE complexes. Aggregated alpha-synuclein is one of the major components found in the Lewy bodies, which are found in the brains of patients with Parkinson’s disease (PD) and other neurodegenerative disorders (1). In fact, there is evidence to suggest that early onset Parkinson's disease may be caused by a duplication or triplication of one of the alpha synuclein genes (2). Alpha-synuclein is also found in the brains of patients with multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS). Recent evidence suggests that phosphorylation of alpha-synuclein at Ser129 plays a role in the formation of inclusions in PD (3,4).

References:

1. Okochi, M. et al: Constitutive phosphorylation of the Parkinson’s disease associated alpha-synuclein. J Biol Chem 2000 Jan 7;275(1): 390-7.

2. Chartier-Harlin, M C. et al: Alpha-synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 2004 364: 1167-1169.

3. Smith, W W. et al: Alpha-synuclein phosphorylation enhances eosinophilic cytoplasmic inclusion formation in SH-SY5Y Cells. J Neurosci 2005 June 8; 25(23):5544-5552.

4. Masliah, E. et al: Effects of alpha-synuclein immunization in a mouse model of Parkinson’s disease. Neuron 2005 Jun 16;46(6):857-868.