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
[41]   MicroRNAs, DNA damage response and ageing [J].
Majidinia, Maryam ;
Mir, Seyed Mostafa ;
Mirza-Aghazadeh-Attari, Mohammad ;
Asghari, Roghaieh ;
Kafil, Hossein Samadi ;
Safa, Amin ;
Mahmoodpoor, Ata ;
Yousefi, Bahman .
BIOGERONTOLOGY, 2020, 21 (03) :275-291
[42]   Targeting miRNAs by polyphenols: Novel therapeutic strategy for aging [J].
Majidinia, Maryam ;
Karimian, Ansar ;
Alemi, Forough ;
Yousefi, Bahman ;
Safa, Amin .
BIOCHEMICAL PHARMACOLOGY, 2020, 173
[43]   p53 is a central regulator driving neurodegeneration caused by C9orf72 poly(PR) [J].
Maor-Nof, Maya ;
Shipony, Zohar ;
Lopez-Gonzalez, Rodrigo ;
Nakayama, Lisa ;
Zhang, Yong-Jie ;
Couthouis, Julien ;
Blum, Jacob A. ;
Castruita, Patricia A. ;
Linares, Gabriel R. ;
Ruan, Kai ;
Ramaswami, Gokul ;
Simon, David J. ;
Nof, Aviv ;
Santana, Manuel ;
Han, Kyuho ;
Sinnott-Armstrong, Nasa ;
Bassik, Michael C. ;
Geschwind, Daniel H. ;
Tessier-Lavigne, Marc ;
Attardi, Laura D. ;
Lloyd, Thomas E. ;
Ichida, Justin K. ;
Gao, Fen-Biao ;
Greenleaf, William J. ;
Yokoyama, Jennifer S. ;
Petrucelli, Leonard ;
Gitler, Aaron D. .
CELL, 2021, 184 (03) :689-+
[44]   ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now? [J].
Mejzini, Rita ;
Flynn, Loren L. ;
Pitout, Lanthe L. ;
Fletcher, Sue ;
Wilton, Steve D. ;
Akkari, P. Anthony .
FRONTIERS IN NEUROSCIENCE, 2019, 13
[45]   ClustVis: a web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap [J].
Metsalu, Tauno ;
Vilo, Jaak .
NUCLEIC ACIDS RESEARCH, 2015, 43 (W1) :W566-W570
[46]   Practice Parameter update: The care of the patient with amyotrophic lateral sclerosis: Drug, nutritional, and respiratory therapies (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology [J].
Miller, R. G. ;
Jackson, C. E. ;
Kasarskis, E. J. ;
England, J. D. ;
Forshew, D. ;
Johnston, W. ;
Kalra, S. ;
Katz, J. S. ;
Mitsumoto, H. ;
Rosenfeld, J. ;
Shoesmith, C. ;
Strong, M. J. ;
Woolley, S. C. .
NEUROLOGY, 2009, 73 (15) :1218-1226
[47]   Pathogenesis of amyotrophic lateral sclerosis [J].
Morgan, Sarah ;
Orrell, Richard W. .
BRITISH MEDICAL BULLETIN, 2016, 119 (01) :87-97
[48]  
MORRIS GM, 2008, METHOD MOL BIOL, V443, P365, DOI DOI 10.1007/978-1-59745-177-2_19
[49]   Serotonin inhibits synaptic glutamate currents in rat nucleus accumbens neurons via presynaptic 5-HT1B receptors [J].
Muramatsu, M ;
Lapiz, MDS ;
Tanaka, E ;
Grenhoff, J .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1998, 10 (07) :2371-2379
[50]   Differentially Expressed miRNAs in Age-Related Neurodegenerative Diseases: A Meta-Analysis [J].
Noronha, Ocana ;
Mesarosovo, Lucia ;
Anink, Jasper J. ;
Iyer, Anand ;
Aronica, Eleonora ;
Mills, James D. .
GENES, 2022, 13 (06)