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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:

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Ubiquitin