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首页> 外文期刊>The European Journal of Neuroscience >The novel cytosolic RING finger protein dactylidin is up-regulated in brains of patients with Alzheimer's disease.
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The novel cytosolic RING finger protein dactylidin is up-regulated in brains of patients with Alzheimer's disease.

机译：阿尔茨海默氏病患者的大脑中新型胞质RING手指蛋白dactylidin上调。

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Abstract Alzheimer's disease (AD) is characterized by a progressive degeneration of neurons along with deposition of amyloid plaques and the formation of neurofibrillary tangles. Neurodegeneration in AD follows both a spatial pattern of selective vulnerability and temporal staging of affected neurons. In order to address transcriptional changes associated with this selective vulnerability, we used subtractive hybridization of transcripts derived from human frontal cortex, which degenerates in late stages of AD, against transcripts of the inferior temporal cortex, which is affected both heavily and early in the course of AD. Moreover, we compared these to brain sections obtained from age-matched control subjects. We isolated a differentially expressed novel gene encoding a polypeptide that contained an amino-terminal C3HC4 RING finger domain, called dactylidin. It is ubiquitously expressed in all tissues examined and in situ hybridization of mouse brain sections revealed specific expression in neurons. Further, heterologous expression studies revealed a cytoplasmic localization of dactylidin and as all known cytoplasmic RING finger proteins function as ubiquitin protein ligases, an E3-like ligase function of dactylidin is probable. However, the up-regulation of dactylidin in highly vulnerable brain tissues of AD patients was confirmed by a quantitative PCR approach, suggesting that dactylidin may function early in the progression of neurodegenerative diseases.
机译：摘要阿尔茨海默氏病（AD）的特征是神经元进行性变性，淀粉样斑块沉积和神经原纤维缠结的形成。 AD中的神经变性遵循选择性脆弱性的空间模式和受影响神经元的时间分期。为了解决与该选择性脆弱性相关的转录变化，我们使用了人类额叶皮层的转录物的减影杂交，该叶在AD的晚期退化，而与颞下皮层的转录本（在此过程中受到严重的影响）的。此外，我们将这些与年龄匹配的对照受试者的大脑切片进行了比较。我们分离了差异表达的新基因，该新基因编码的多肽包含一个氨基末端C3HC4 RING手指结构域，称为Dactylidin。它在所有检查过的组织中普遍表达，小鼠大脑切片的原位杂交揭示了神经元中的特异性表达。此外，异源表达研究揭示了猕猴桃素的细胞质定位，并且由于所有已知的胞质RING指蛋白起泛素蛋白连接酶的作用，因此，仙人掌素可能具有E3样连接酶的功能。然而，通过定量PCR方法证实了AD患者高度脆弱的脑组织中的Dactylidin上调，这表明Dactylidin可能在神经退行性疾病发展的早期起作用。

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