肌萎缩性侧索硬化症中microrna的差异表达和预测药物靶点

IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Molecular Neuroscience Pub Date : 2023-05-30 DOI:10.1007/s12031-023-02124-z
Riya Ben Patel, Akhilesh Kumar Bajpai, Kavitha Thirumurugan
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引用次数: 0

摘要

肌萎缩性侧索硬化症是一种罕见的神经退行性疾病。它显示了大脑和脊髓中运动神经元的逐渐退化。目前,还没有可以完全治愈ALS的治疗方法。现有的治疗方法只能将病人的寿命延长几个月。最近,小非编码rna的一个亚类microRNAs (miRNAs)已被证明在ALS的诊断、预后和治疗中发挥重要作用。我们的研究重点是利用生物信息学和计算方法分析ALS的差异miRNA谱和预测药物靶点。该研究确定了ALS患者中8个高度差异表达的mirna,其中4个是新的。通过蛋白-蛋白相互作用网络和Cytoscape分析,我们确定了这8个高表达miRNA的42个枢纽基因,其中淀粉样蛋白前体蛋白(APP)作为高表达下调miRNA hsa-miR-455-3p的候选基因。利用KEGG通路分析发现hsa-miR-455-3p/APP/ 5-羟色胺能通路之间存在新的关联。此外,分子对接研究显示姜黄素可能是治疗ALS的潜在药物靶点。因此,本研究确定了四种新的miRNA生物标志物:hsa-miR-3613-5p、hsa-miR-24、hsa-miR-3064-5p和hsa-miR-4455。形成了一个新的轴,hsa-miR-455-3p/APP/ 5-羟色胺能通路,姜黄素被预测为ALS的潜在药物靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Differential Expression of MicroRNAs and Predicted Drug Target in Amyotrophic Lateral Sclerosis

ALS (Amyotrophic Lateral Sclerosis) is a rare type of neurodegenerative disease. It shows progressive degradation of motor neurons in the brain and spinal cord. At present, there is no treatment available that can completely cure ALS. The available treatments can only increase a patient’s life span by a few months. Recently, microRNAs (miRNAs), a sub-class of small non-coding RNAs have been shown to play an essential role in the diagnosis, prognosis, and therapy of ALS. Our study focuses on analyzing differential miRNA profiles and predicting drug targets in ALS using bioinformatics and computational approach. The study identifies eight highly differentially expressed miRNAs in ALS patients, four of which are novel. We identified 42 hub genes for these eight highly expressed miRNAs with Amyloid Precursor Protein (APP) as a candidate gene among them for highly expressed down-regulated miRNA, hsa-miR-455-3p using protein–protein interaction network and Cytoscape analysis. A novel association has been found between hsa-miR-455-3p/APP/serotonergic pathway using KEGG pathway analysis. Also, molecular docking studies have revealed curcumin as a potential drug target that may be used for the treatment of ALS. Thus, the present study has identified four novel miRNA biomarkers: hsa-miR-3613-5p, hsa-miR-24, hsa-miR-3064-5p, and hsa-miR-4455. There is a formation of a novel axis, hsa-miR-455-3p/APP/serotonergic pathway, and curcumin is predicted as a potential drug target for ALS.

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来源期刊
Journal of Molecular Neuroscience
Journal of Molecular Neuroscience 医学-神经科学
CiteScore
6.60
自引率
3.20%
发文量
142
审稿时长
1 months
期刊介绍: The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.
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