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MicroRNA Expression Signature in Mild Cognitive Impairment Due to Alzheimer's Disease.
Molecular Neurobiology ( IF 4.6 ) Pub Date : 2020-07-31 , DOI: 10.1007/s12035-020-02029-7
Bruna De Felice 1 , Concetta Montanino 1 , Mariano Oliva 2 , Simona Bonavita 2 , Valeria Di Onofrio 3 , Cinzia Coppola 2
Affiliation  

Mild cognitive impairment (MCI) defines an intermediate state between normal ageing and dementia, including Alzheimer’s disease (AD). Identification of MCI subjects who will progress to AD (MCI-AD) is today of crucial importance, especially in light of the possible development of new pathogenic therapies. Several evidences suggest that miRNAs could play relevant roles in the biogenesis of AD, and the links between selected miRNAs and specific pathogenic aspects have been partly explored. In this study, we analysed the composition of microRNA transcriptome in blood, serum and cerebrospinal fluid samples from MCI-AD subjects, from an enriched small RNA library. Real-time qPCR from MCI-AD and AD patients and normal controls was performed to profile miRNA expression. In particular, four microRNAs, hsa-mir-5588-5p, hsa-mir-3658, hsa-mir-567 and hsa-mir-3908, among all selected microRNAs, are dysregulated. Hsa-mir-567 was found to be differentially expressed in cerebrospinal fluid samples, blood and serum from MCI-AD patients, showing the highest fold change and statistical significance. Target prediction analysis have been performed to evaluate mRNAs whose expression was controlled by miRNAs found to be dysregulated here, showing that hsa-mir-567 target genes are functionally active in neuronal cells. We propose that miRNA profiles found in samples from MCI-AD patients might be relevant for a better understanding of AD-related cognitive decline and could lead to set up suitable and potential biomarkers for MCI-AD progression to AD.



中文翻译:

由于阿尔茨海默氏病引起的轻度认知障碍中的MicroRNA表达特征。

轻度认知障碍(MCI)定义了正常衰老和痴呆症之间的一种中间状态,包括阿尔茨海默氏病(AD)。如今,特别是考虑到可能会发展出新的病原学疗法,确定将要发展为AD的MCI受试者(MCI-AD)至关重要。若干证据表明,miRNA可能在AD的生物发生中发挥相关作用,并且已部分探索了所选miRNA与特定致病因素之间的联系。在这项研究中,我们分析了MCI-AD受试者血液中,血清和脑脊液样品中microRNA转录组的组成,这些样品来自丰富的小RNA库。进行了来自MCI-AD和AD患者以及正常对照的实时qPCR,以分析miRNA的表达。特别是,四个microRNA,即hsa-mir-5588-5p,hsa-mir-3658,在所有选定的microRNA中,hsa-mir-567和hsa-mir-3908失调。发现Hsa-mir-567在MCI-AD患者的脑脊液样本,血液和血清中差异表达,显示最高的倍数变化和统计学意义。已经进行了靶标预测分析,以评估其表达受此处失调的miRNA所控制的mRNA,这表明hsa-mir-567靶标基因在神经元细胞中具有功能活性。我们建议在MCI-AD患者的样本中发现的miRNA谱可能与更好地了解AD相关的认知功能下降有关,并且可能导致建立合适的和潜在的MCI-AD进展为AD的生物标记。MCI-AD患者的血液和血清,显示最高的倍数变化和统计学意义。已经进行了靶标预测分析,以评估其表达受此处失调的miRNA所控制的mRNA,这表明hsa-mir-567靶标基因在神经元细胞中具有功能活性。我们建议在MCI-AD患者的样本中发现的miRNA谱可能与更好地了解AD相关的认知功能下降有关,并且可能导致建立合适的和潜在的MCI-AD进展为AD的生物标记。MCI-AD患者的血液和血清,显示最高的倍数变化和统计学意义。已经进行了靶标预测分析,以评估其表达受此处失调的miRNA所控制的mRNA,这表明hsa-mir-567靶标基因在神经元细胞中具有功能活性。我们建议在MCI-AD患者的样本中发现的miRNA谱可能与更好地了解AD相关的认知功能下降有关,并且可能导致建立合适的和潜在的MCI-AD进展为AD的生物标记。表明hsa-mir-567靶基因在神经元细胞中具有功能活性。我们建议在MCI-AD患者的样本中发现的miRNA谱可能与更好地了解AD相关的认知功能下降有关,并且可能导致建立合适的和潜在的MCI-AD进展为AD的生物标记。表明hsa-mir-567靶基因在神经元细胞中具有功能活性。我们建议在MCI-AD患者的样本中发现的miRNA谱可能与更好地了解AD相关的认知功能下降有关,并且可能导致建立合适的和潜在的MCI-AD进展为AD的生物标记。

更新日期:2020-09-24
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