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神经退行性疾病中的基因网络。

Gene networks in neurodegenerative disorders.

作者信息

Recabarren Daniela, Alarcón Marcelo

机构信息

Parral, Maule, 3630000, Chile.

Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Universidad de Talca, Talca 3460000, Chile; Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Universidad de Talca, Talca 3460000, Chile.

出版信息

Life Sci. 2017 Aug 15;183:83-97. doi: 10.1016/j.lfs.2017.06.009. Epub 2017 Jun 13.

Abstract

Three neurodegenerative diseases [Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD)] have many characteristics like pathological mechanisms and genes. In this sense some researchers postulate that these diseases share the same alterations and that one alteration in a specific protein triggers one of these diseases. Analyses of gene expression may shed more light on how to discover pathways, pathologic mechanisms associated with the disease, biomarkers and potential therapeutic targets. In this review, we analyze four microarrays related to three neurodegenerative diseases. We will systematically examine seven genes (CHN1, MDH1, PCP4, RTN1, SLC14A1, SNAP25 and VSNL1) that are altered in the three neurodegenerative diseases. A network was built and used to identify pathways, miRNA and drugs associated with ALS, AD and PD using Cytoscape software an interaction network based on the protein interactions of these genes. The most important affected pathway is PI3K-Akt signalling. Thirteen microRNAs (miRNA-19B1, miRNA-107, miRNA-124-1, miRNA-124-2, miRNA-9-2, miRNA-29A, miRNA-9-3, miRNA-328, miRNA-19B2, miRNA-29B2, miRNA-124-3, miRNA-15A and miRNA-9-1) and four drugs (Estradiol, Acetaminophen, Resveratrol and Progesterone) for new possible treatments were identified.

摘要

三种神经退行性疾病[肌萎缩侧索硬化症(ALS)、帕金森病(PD)和阿尔茨海默病(AD)]具有许多共同特征,如病理机制和相关基因。从这个意义上说,一些研究人员推测这些疾病存在相同的病变,且特定蛋白质的一种病变会引发其中一种疾病。基因表达分析可能会为发现疾病相关途径、病理机制、生物标志物和潜在治疗靶点提供更多线索。在本综述中,我们分析了与三种神经退行性疾病相关的四个微阵列。我们将系统研究在这三种神经退行性疾病中发生改变的七个基因(CHN1、MDH1、PCP4、RTN1、SLC14A1、SNAP25和VSNL1)。构建了一个网络,并使用Cytoscape软件(基于这些基因的蛋白质相互作用的相互作用网络)来识别与ALS、AD和PD相关的途径、miRNA和药物。受影响最重要的途径是PI3K-Akt信号通路。确定了13种微小RNA(miRNA-19B1、miRNA-107、miRNA-124-1、miRNA-124-2、miRNA-9-2、miRNA-29A、miRNA-9-3、miRNA-328、miRNA-19B2、miRNA-29B2、miRNA-124-3、miRNA-15A和miRNA-9-1)和四种可能用于新治疗方法的药物(雌二醇、对乙酰氨基酚、白藜芦醇和孕酮)。

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