Alpha-synuclein expression in substantia nigra and cortex in Parkinson's disease

Mov Disord. 1999 May;14(3):417-22. doi: 10.1002/1531-8257(199905)14:3<417::aid-mds1005>;2-x.


Mutations in the human alpha-synuclein gene have been identified in several families of European descent with early-onset Parkinson's disease (PD). We sequenced the complete alpha-synuclein cDNA from substantia nigra and cortex from nine patients with PD and eight control subjects. No mutations were found. We then analyzed alpha-synuclein mRNA levels using a ribonuclease protection assay. Two major protected bands of alpha-synuclein mRNA, possibly representing two splice variants of the gene, were observed. Alpha-synuclein mRNA was significantly diminished in the substantia nigra of patients with PD compared with control subjects but not in the cortex. Our findings suggest that decreased synuclein mRNA may be an early alteration in the SN in PD, and imply that decreased levels of the protein may play a role in the pathogenesis of sporadic cases of the disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cerebral Cortex / metabolism*
  • DNA, Recombinant / genetics
  • Female
  • Gene Expression / genetics*
  • Humans
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics*
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism*
  • Phosphoproteins / biosynthesis*
  • Phosphoproteins / genetics*
  • Point Mutation / genetics*
  • Substantia Nigra / metabolism*
  • Synucleins
  • alpha-Synuclein


  • DNA, Recombinant
  • Nerve Tissue Proteins
  • Phosphoproteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein