Analysis of striatal transcriptome in mice overexpressing human wild-type alpha-synuclein supports synaptic dysfunction and suggests mechanisms of neuroprotection for striatal neurons.
Analysis of striatal transcriptome in mice overexpressing human wild-type alpha-synuclein supports synaptic dysfunction and suggests mechanisms of neuroprotection for striatal neurons.
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DOI：
10.1186/1750-1326-6-83
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发表时间：
2011-12-13
影响因子：
15.1
通讯作者：
Schiestl RH
中科院分区：
文献类型：
--
作者：
Cabeza-Arvelaiz Y;Fleming SM;Richter F;Masliah E;Chesselet MF;Schiestl RH
α突触核蛋白(SNCA)与包括帕金森氏病(PD)在内的神经退行性疾病(突触核病症)有关。虽然帕金森病的原发神经变性涉及黑质纹状体多巴胺能神经元，但在其他联核病中也观察到更广泛的局部选择性神经变性。此外，SNCA在神经元中广泛表达，在帕金森病患者中许多神经系统功能障碍。因此，了解SNCA的过度表达如何影响帕金森病患者中非直接针对神经变性的区域的神经元功能是很有意义的。本研究通过转录组分析，研究了在Thy1启动子下过度表达野生型人SNCA的小鼠(Thy1-aSyn小鼠)纹状体内SNCA过表达对细胞过程和功能的影响。分析揭示了Thy1-aSyn小鼠纹状体中多种生物学过程的变化，包括突触可塑性、信号、转录、凋亡和神经发生。这些结果支持SNCA在突触功能中的关键作用，并揭示了Thy1-aSyn小鼠的细胞凋亡特征，这与神经保护基因的特异性变化一起表明，在SNCA神经元过度表达的情况下，激活了可能保护纹状体神经元的适应性代偿机制。
Alpha synuclein (SNCA) has been linked to neurodegenerative diseases (synucleinopathies) that include Parkinson's disease (PD). Although the primary neurodegeneration in PD involves nigrostriatal dopaminergic neurons, more extensive yet regionally selective neurodegeneration is observed in other synucleinopathies. Furthermore, SNCA is ubiquitously expressed in neurons and numerous neuronal systems are dysfunctional in PD. Therefore it is of interest to understand how overexpression of SNCA affects neuronal function in regions not directly targeted for neurodegeneration in PD. The present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice) by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis. The results support a key role for SNCA in synaptic function and revealed an apoptotic signature in Thy1-aSyn mice, which together with specific alterations of neuroprotective genes suggest the activation of adaptive compensatory mechanisms that may protect striatal neurons in conditions of neuronal overexpression of SNCA.
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影响因子：
11.4
作者：
Crameri, A;Biondi, E;Mohajeri, MH
通讯作者：
Mohajeri, MH
影响因子：
6.1
作者：
Cantuti-Castelvetri, Ippolita;Keller-McGandy, Christine;Standaert, David G.
通讯作者：
Standaert, David G.
DOI：
10.1152/ajpendo.00262.2010
发表时间：
2011-02-01
影响因子：
5.1
作者：
Geng, Xuehui;Lou, Haiyan;Drain, Peter
通讯作者：
Drain, Peter
影响因子：
6.4
作者：
Di Stasi, D;Vallacchi, V;Rodolfo, M
通讯作者：
Rodolfo, M
DOI：
10.1111/j.1460-9568.2008.06346.x
发表时间：
2008-07
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Fleming SM;Tetreault NA;Mulligan CK;Hutson CB;Masliah E;Chesselet MF
通讯作者：
Chesselet MF