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

被引:2
作者
Patel, Riya Ben [1 ]
Bajpai, Akhilesh Kumar [2 ]
Thirumurugan, Kavitha [1 ]
机构
[1] Vellore Inst Technol, Sch Biosci & Technol, Struct Biol Lab, 412J,Pearl Res Pk, Vellore 632014, India
[2] Univ Tennessee, Hlth Sci Ctr, Dept Genet Genom & Informat, Memphis, TN 38163 USA
关键词
Amyotrophic lateral sclerosis; MicroRNAs; Microarray data; Target genes; Drug targets; SKELETAL-MUSCLE; SYSTEM; GENES; ENVIRONMENT; MECHANISMS; THERAPIES; UPDATE; MIRNAS; TOOL; ALS;
D O I
10.1007/s12031-023-02124-z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:375 / 390
页数:16
相关论文
共 80 条
[11]   Muscle histone deacetylase 4 upregulation in amyotrophic lateral sclerosis: potential role in reinnervation ability and disease progression [J].
Bruneteau, Gaelle ;
Simonet, Thomas ;
Bauche, Stephanie ;
Mandjee, Nathalie ;
Malfatti, Edoardo ;
Girard, Emmanuelle ;
Tanguy, Marie-Laure ;
Behin, Anthony ;
Khiami, Frederic ;
Sariali, Elhadi ;
Hell-Remy, Caroline ;
Salachas, Francois ;
Pradat, Pierre-Francois ;
Fournier, Emmanuel ;
Lacomblez, Lucette ;
Koenig, Jeanine ;
Romero, Norma Beatriz ;
Fontaine, Bertrand ;
Meininger, Vincent ;
Schaeffer, Laurent ;
Hantai, Daniel .
BRAIN, 2013, 136 :2359-2368
[12]   Amyloid precursor protein (APP) contributes to pathology in the SOD1G93A mouse model of amyotrophic lateral sclerosis [J].
Bryson, J. Barney ;
Hobbs, Carl ;
Parsons, Michael J. ;
Bosch, Karen D. ;
Pandraud, Amelie ;
Walsh, Frank S. ;
Doherty, Patrick ;
Greensmith, Linda .
HUMAN MOLECULAR GENETICS, 2012, 21 (17) :3871-3882
[13]   Antioxidant Alternatives in the Treatment of Amyotrophic Lateral Sclerosis: A Comprehensive Review [J].
Carrera-Julia, Sandra ;
Moreno, Mari Luz ;
Barrios, Carlos ;
de la Rubia Orti, Jose Enrique ;
Drehmer, Eraci .
FRONTIERS IN PHYSIOLOGY, 2020, 11
[14]   A framework for oligonucleotide microarray preprocessing [J].
Carvalho, Benilton S. ;
Irizarry, Rafael A. .
BIOINFORMATICS, 2010, 26 (19) :2363-2367
[15]   Defective Proteasome Delivery of Polyubiquitinated Proteins by Ubiquilin-2 Proteins Containing ALS Mutations [J].
Chang, Lydia ;
Monteiro, Mervyn J. .
PLOS ONE, 2015, 10 (06)
[16]  
Chen JJ, 2020, AM J MANAG CARE, V26, pS191, DOI 10.37765/ajmc.2020.88483
[17]   Amyotrophic Lateral Sclerosis and Oxidative Stress: A Double-blind Therapeutic Trial after Curcumin Supplementation [J].
Chico, Lucia ;
Ienco, Elena Caldarazzo ;
Bisordi, Costanza ;
Lo Gerfo, Annalisa ;
Petrozzi, Lucia ;
Petrucci, Antonio ;
Mancuso, Michelangelo ;
Siciliano, Gabriele .
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS, 2018, 17 (10) :767-779
[18]   cytoHubba: identifying hub objects and sub-networks from complex interactome [J].
Chin, Chia-Hao ;
Chen, Shu-Hwa ;
Wu, Hsin-Hung ;
Ho, Chin-Wen ;
Ko, Ming-Tat ;
Lin, Chung-Yen .
BMC SYSTEMS BIOLOGY, 2014, 8
[19]   Development and evaluation of a clinical staging system for amyotrophic lateral sclerosis [J].
Chio, Adriano ;
Hammond, Edward R. ;
Mora, Gabriele ;
Bonito, Virginio ;
Filippini, Graziella .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2015, 86 (01) :38-44
[20]  
Clough E, 2016, METHODS MOL BIOL, V1418, P93, DOI 10.1007/978-1-4939-3578-9_5