Does α-synuclein have a dual and opposing effect in preclinical vs. clinical Parkinson's disease?
Does α-synuclein have a dual and opposing effect in preclinical vs. clinical Parkinson's disease?
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DOI：
10.1016/j.parkreldis.2014.02.021
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发表时间：
2014-06-01
影响因子：
4.1
通讯作者：
Maraganore, Demetrius M.
中科院分区：
文献类型：
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作者：
Markopoulou, Katerina;Biernacka, Joanna M.;Maraganore, Demetrius M.
α-突触核蛋白基因（SNCA）倍增引起家族性帕金森综合征，并且SNCA二核苷酸重复REP 1内的等位基因长度多态性增加发展帕金森病（PD）的风险。由于SNCA倍增增加SNCA表达，并且增加发展PD风险的REP 1基因型在细胞培养系统、动物模型以及人血液和脑中显示SNCA表达增加，因此PD疗法寻求减少SNCA表达。我们对1098例PD病例进行了一项观察性研究，以检验与SNCA表达减少相关的REP 1基因型与更好的运动和认知结果相关的假设。我们评估了REP 1基因型与Hoehn和Yahr 4或5级（运动结果）和改良的认知状态电话访谈评分的生存率之间的关系。
a-Synuclein gene (SNCA) multiplications cause familial parkinsonism and allele-length polymorphisms within the SNCA dinucleotide repeat REP1 increase the risk for developing Parkinson's disease (PD). Since SNCA multiplications increase SNCA expression, and REP1 genotypes that increase the risk of developing PD show increased SNCA expression in cell-culture systems, animal models, and human blood and brain, PD therapies seek to reduce SNCA expression. We conducted an observational study of 1098 PD cases to test the hypothesis that REP1 genotypes correlated with reduced SNCA expression are associated with better motor and cognitive outcomes. We evaluated the association of REP1 genotypes with survival free of Hoehn and Yahr stages 4 or 5 (motor outcome) and of Modified Telephone Interview for Cognitive Status score