The pre-synaptic protein alpha-synuclein is the main component of Lewy bodies 
and Lewy neurites, the defining neuropathological characteristics of Parkinson's 
disease and dementia with Lewy bodies. Mutations in the alpha-synuclein gene 
cause familial forms of Parkinson's disease and dementia with Lewy bodies. We 
previously described a transgenic mouse line expressing truncated human 
alpha-synuclein(1-120) that develops alpha-synuclein aggregates, striatal 
dopamine deficiency and reduced locomotion, similar to Parkinson's disease. We 
now show that in the striatum of these mice, as in Parkinson's disease, synaptic 
accumulation of alpha-synuclein is accompanied by an age-dependent 
redistribution of the synaptic SNARE proteins SNAP-25, syntaxin-1 and 
synaptobrevin-2, as well as by an age-dependent reduction in dopamine release. 
Furthermore, the release of FM1-43 dye from PC12 cells expressing either human 
full-length alpha-synuclein(1-140) or truncated alpha-synuclein(1-120) was 
reduced. These findings reveal a novel gain of toxic function of alpha-synuclein 
at the synapse, which may be an early event in the pathogenesis of Parkinson's 
disease.