Synuclein

Chromosome 4: SNCA gene: 112 kb

mRNA with exon2+3+4+5+6 -> alpha synuclein (140AA)

mRNA with exon2+4+5+6 -> alpha synuclein (126 AA)

mRNA with exon2+3+4+6 -> alpha synuclein (112 AA)

Sequence of syuclein and location of the two mutations responsible of rare familial forms of Parkinson's disease.

Sequence, mutations and post-translational events

Physiological role: presynaptic protein involved in neuronal plasticity

Physiopathology: 

• aggregated in numerous neurodegenerative disorders, named alpha-synucleinopathies, and in particular in Lewy bodies found in Parkinson disease (and in  dementia with Lewy bodies).
• degraded by proteosome, via ubiquitination
• modified on tyrosine by oxidative nitration
• cerebral lesions: Lewy bodies, Lewy neurites, GCI (glial cytoplasmic inclusions)

Alpha-synucleopathies:

• Parkinson disease, Parkinson disease with dementia
• dementia with Lewy bodies
• multiple system atrophy
• Hallenvordern-Spatz diease
• found also in Alzheimer's disease