Levels of alpha-synuclein mRNA in sporadic Parkinson disease patients

被引:131
作者
Chiba-Falek, Ornit [1 ]
Lopez, Grisel J. [1 ]
Nussbaum, Robert L. [1 ]
机构
[1] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA
关键词
alpha-synuclein; Parkinson disease; SNCA-mRNA; real-time PCR;
D O I
10.1002/mds.21007
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 a-synuclein (SNCA) has been shown to cause early-onset familial PD. However, it is not clear whether increased a-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 a-synuclein expression is associated, among other factors, with the development of sporadic PD. (C) 2006 Movement Disorder Society.
引用
收藏
页码:1703 / 1708
页数:6
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