Levels of alpha-synuclein mRNA in sporadic Parkinson disease patients.
Lewy bodies, the pathological hallmark of Parkinson's disease (PD), consist largely of alpha-synuclein, a 14.5-kDa presynaptic neuronal protein implicated in familial PD. An increased copy number and elevated expression of wild-type alpha-synuclein (SNCA) has been shown to cause early-onset familial PD. However, it is not clear whether increased alpha-synuclein expression also plays a role in the pathogenesis of sporadic disease. In the current study, we analyzed the levels of SNCA-mRNA in affected brains of sporadic PD patients. We compared the levels of steady state SNCA-mRNA in 7 sporadic PD brain samples and 7 normal controls using real-time polymerase chain reaction of RNA extracted from mid-brain tissue, including the substantia nigra. Despite that there is neuronal loss in the substantia nigra of PD brains, overall the SNCA-mRNA levels were increased in PD brains an average of nearly fourfold over normal control mid-brain, although there was much greater variability in samples from PD patients compared to controls. Frontal cortex samples from selected individuals were also analyzed. SNCA-mRNA levels were not significantly changed in PD frontal cortex compared to controls. These results suggest that elevated expression levels of SNCA-mRNA are found in the affected regions of PD brain and support the hypothesis that increases in alpha-synuclein expression is associated, among other factors, with the development of sporadic PD.
Chiba-Falek
Ornit
O
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Lopez
Grisel J
GJ
Nussbaum
Robert L
RL
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015870:Gene Expression / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D010300:Parkinson Disease / Q000175:diagnosis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012016:Reference Values; D013378:Substantia Nigra / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics*
D012333:RNA, Messenger; C497604:SNCA protein, human; D051844:alpha-Synuclein