A synaptic protein found in aggregates (Lewy bodies) in Parkinson's disease and Dementia with Lewy Bodies. It is also found as inclusions in the neuroglial in multiple system atrophy and in other abnormal disposition in several other neurodegenerative diseases of the central nervous system. It has recently been postulated that presynaptic alpha-synuclein aggregates may actually be the common association. Accumulation of alpha-synuclein in cultured human dopaminergic neurons exposed to dopamine and oxygen radicals results in apoptosis. Alpha-synuclein is not toxic in nondopaminergic human cortical neurons.
Mutations of alpha-synuclein gene (SNCA) at 4q21 cause some familial Parkinson's disease:
- PARK1 - various point mutations eg ala53-to-thr (A53T), ala30-to-pro (A30P) substitution and SNCA duplication.
- PARK4 - triplication
- Autosomal dominant Lewy body dementia - glu46-to-lys (E46K) mutation
- ↑ Kramer ML, Schulz-Schaeffer WJ. Presynaptic alpha-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies. The Journal of neuroscience : the official journal of the Society for Neuroscience 2007;27:1405-10. (Direct link – subscription may be required.)
- ↑ Xu J, Kao SY, Lee FJ, Song W, Jin LW, Yankner BA. Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nature medicine 2002;8:600-6. (Direct link – subscription may be required.)