Differential expression of alpha-synuclein, parkin, and synphilin-1 isoforms in Lewy body disease
Differential expression of alpha-synuclein, parkin, and synphilin-1 isoforms in Lewy body disease
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DOI：
10.1007/s10048-008-0124-6
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发表时间：
2008-07-01
期刊：
影响因子：
2.2
通讯作者：
Ariza, Aurelio
中科院分区：
文献类型：
--
作者：
Beyer, Katrin;Domingo-Sabat, Montserrat;Ariza, Aurelio
α-突触核蛋白、帕金蛋白和突触亲蛋白-1是主要参与路易体（LB）疾病的发病机制的蛋白质。所有这三种基因的mRNA都经历了选择性剪接，因此已经描述了各种异构体的存在。由于越来越多的证据支持差异亚型表达变化在疾病发展中的重要性，我们已经建立了LB疾病大脑额叶皮质中的亚型表达谱与阿尔茨海默病（AD）和控制额叶皮质相比。通过使用同种型特异性引物和以SybrGreen和β-肌动蛋白作为内标的相对表达分析，确定了4种α-突触核蛋白、7种帕金蛋白和4种突触亲蛋白-1同种型的差异表达。异构体表达谱的建立揭示了这些是疾病特异性的。此外，在每种疾病中主要可以观察到一个基因的异构体表达失调。所有四种α-突触核蛋白亚型在单纯型LB痴呆、常见LB疾病中的大多数帕金转录物变体和帕金森病中的所有突触亲蛋白-1亚型的情况下都受到影响。在AD中仅检测到轻微受累。最后，在常见的LB疾病中存在专有的同种型表达谱表明，这种疾病的发展是其自身分子机制的结果，因此，在分子水平上，它并不完全共享在LB和AD的纯痴呆中发现的变化。总之，在LB疾病中的亚型表达谱代表了在神经退行性疾病的发展中亚型表达失调直接参与的额外证据。
Alpha-synuclein, parkin, and synphilin-1 are proteins mainly involved in the pathogenesis of Lewy body (LB) diseases. mRNAs of all three undergo alternative splicing, so that the existence of various isoforms has been described. Since increasing evidence supports the importance of differential isoform-expression changes in disease development, we have established isoform-expression profiles in frontal cortices of LB disease brains in comparison with those of Alzheimer disease (AD) and control frontal cortices. The differential expression of four alpha-synuclein, seven parkin, and four synphilin-1 isoforms was ascertained by the use of isoform-specific primers and relative expression analysis with SybrGreen and beta-actin as an internal standard. The establishment of isoform-expression profiles revealed that these are disease specific. Moreover, isoform-expression deregulation of mainly one gene in each disease could be observed. All four alpha-synuclein isoforms were affected in the case of the pure form of dementia with LB, most parkin transcript variants in common LB disease, and all synphilin-1 isoforms in Parkinson disease. Only minor involvement was detected in AD. Finally, the existence of a proprietary isoform-expression profile in common LB disease indicates that this disease develops as a result of its own molecular mechanisms, and so, at the molecular level, it does not exactly share changes found in pure dementia with LB and AD. In conclusion, isoform-expression profiles in LB diseases represent additional evidence for the direct involvement of isoform-expression deregulation in the development of neurodegenerative disorders.