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诱导多能干细胞衍生的神经元细胞作为阿尔茨海默病诊断和治疗预测指标的探索性分析

Exploratory Analysis of iPSCS-Derived Neuronal Cells as Predictors of Diagnosis and Treatment of Alzheimer Disease.

作者信息

Cavalli Eugenio, Battaglia Giuseppe, Basile Maria Sofia, Bruno Valeria, Petralia Maria Cristina, Lombardo Salvo Danilo, Pennisi Manuela, Kalfin Reni, Tancheva Lyubka, Fagone Paolo, Nicoletti Ferdinando, Mangano Katia

机构信息

Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy.

University Sapienza, Piazzale A. Moro, 5, 00185 Roma, Italy.

出版信息

Brain Sci. 2020 Mar 13;10(3):166. doi: 10.3390/brainsci10030166.

Abstract

Alzheimer's disease (AD) represents the most common neurodegenerative disorder, with 47 million affected people worldwide. Current treatment strategies are aimed at reducing the symptoms and do slow down the progression of the disease, but inevitably fail in the long-term. Induced pluripotent stem cells (iPSCs)-derived neuronal cells from AD patients have proven to be a reliable model for AD pathogenesis. Here, we have conducted an in silico analysis aimed at identifying pathogenic gene-expression profiles and novel drug candidates. The GSE117589 microarray dataset was used for the identification of Differentially Expressed Genes (DEGs) between iPSC-derived neuronal progenitor (NP) cells and neurons from AD patients and healthy donors. The Discriminant Analysis Module (DAM) algorithm was used for the identification of biomarkers of disease. Drugs with anti-signature gene perturbation profiles were identified using the L1000FWD software. DAM analysis was used to identify a list of potential biomarkers among the DEGs, able to discriminate AD patients from healthy people. Finally, anti-signature perturbation analysis identified potential anti-AD drugs. This study set the basis for the investigation of potential novel pharmacological strategies for AD. Furthermore, a subset of genes for the early diagnosis of AD is proposed.

摘要

阿尔茨海默病(AD)是最常见的神经退行性疾病,全球有4700万人受其影响。目前的治疗策略旨在减轻症状并确实减缓疾病进展,但从长期来看不可避免地会失败。来自AD患者的诱导多能干细胞(iPSC)衍生的神经元细胞已被证明是AD发病机制的可靠模型。在此,我们进行了一项计算机分析,旨在识别致病基因表达谱和新型候选药物。GSE117589微阵列数据集用于识别AD患者和健康供体的iPSC衍生的神经祖细胞(NP)与神经元之间的差异表达基因(DEG)。判别分析模块(DAM)算法用于识别疾病生物标志物。使用L1000FWD软件识别具有抗特征基因扰动谱的药物。DAM分析用于在DEG中识别能够区分AD患者和健康人的潜在生物标志物列表。最后,抗特征扰动分析确定了潜在的抗AD药物。本研究为研究AD潜在的新型药理学策略奠定了基础。此外,还提出了一组用于AD早期诊断的基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61d/7139610/53c57a2c545c/brainsci-10-00166-g001.jpg

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