#412J, Structural Biology Lab, Pearl Research Park, School of Biosciences & Technology, Vellore Institute of Technology, Vellore-632014, India.
Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
J Mol Neurosci. 2023 Jun;73(6):375-390. doi: 10.1007/s12031-023-02124-z. Epub 2023 May 30.
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.
肌萎缩侧索硬化症（ALS）是一种罕见的神经退行性疾病。它表现为大脑和脊髓中的运动神经元进行性退化。目前，尚无可完全治愈 ALS 的治疗方法。现有的治疗方法只能使患者的寿命延长几个月。最近，miRNAs（miRNA），一种小的非编码 RNA 亚类，已被证明在 ALS 的诊断、预后和治疗中发挥着重要作用。我们的研究集中在使用生物信息学和计算方法分析 ALS 中的差异 miRNA 图谱和预测药物靶点。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。我们使用蛋白质-蛋白质相互作用网络和 Cytoscape 分析，确定了这 8 个高度表达 miRNA 的 42 个核心基因，其中 APP 作为候选基因，在高度表达下调的 miRNA，hsa-miR-455-3p 中。KEGG 途径分析发现了 hsa-miR-455-3p/APP/5-羟色胺能途径之间的新关联。此外，分子对接研究表明姜黄素可能是一种潜在的药物靶点，可用于治疗 ALS。因此，本研究确定了 4 个新的 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-羟色胺能途径，并且姜黄素被预测为 ALS 的潜在药物靶点。
