title: Alpha-synuclein expression in substantia nigra and cortex in Parkinson's disease.
abstract: 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.
authors.affiliation: Department of Neurology, College of Physicians & Surgeons, Columbia University, Columbia-Presbyterian Medical Center, New York, NY 10032, USA.
authors.forename: M
authors.initials: M
authors.lastname: Neystat
authors.forename: T
authors.initials: T
authors.lastname: Lynch
authors.forename: S
authors.initials: S
authors.lastname: Przedborski
authors.forename: N
authors.initials: N
authors.lastname: Kholodilov
authors.forename: M
authors.initials: M
authors.lastname: Rzhetskaya
authors.forename: R E
authors.initials: RE
authors.lastname: Burke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002540:Cerebral Cortex / Q000378:metabolism*; D004274:DNA, Recombinant / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism*; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D013378:Substantia Nigra / Q000378:metabolism*; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D004274:DNA, Recombinant; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein