MINI-REVIEW OF NUCLEAR-FACTOR-KAPPA-B IN SILICO STUDIES
Received: 23rd August 2024 Revised: 1st September 2024, 8th September 2024 Accepted: 26th August 2024
DOI:
https://doi.org/10.20319/lijhls.2024.10.0111Keywords:
Nuclear Factor Kappa B, In Silico, Signalling Pathway, Inflammation, Immune ResponseAbstract
This mini-review provides a concise overview of the advancements in computer-assisted methodologies and research related to nuclear factor kappa B (NF-kB) over the past decade. Applying computer-aided or in silico methods to investigating the NF-kB complex offers intriguing options for identifying treatment targets for various disorders involving the NF-kB protein. Compared to traditional in vivo and in vitro investigations, in silico research has multiple advantages, including improved precision, increased efficiency, and eliminating the requirement for human and animal participants. This method creates a framework for evaluating the efficacy of potential treatments against specific molecular targets, allowing for the prediction of their efficacy based on the structural properties of compounds before synthesis for subsequent in vitro and in vivo testing. Targeting the NF-kB protein is critical because it plays a role in many disorders involving immunological and inflammatory responses, stress responses, cellular proliferation, and apoptosis. These findings are essential for guiding future research into the role of the NF-kB protein in human disorders and identifying possible therapeutic targets.
This mini-review provides a concise overview of the advancements in computer-assisted methodologies and research related to nuclear factor kappa B (NF-kB) over the past decade. Applying computer-aided or in silico methods to investigating the NF-kB complex offers intriguing options for identifying treatment targets for various disorders involving the NF-kB protein. Compared to traditional in vivo and in vitro investigations, in silico research has multiple advantages, including improved precision, increased efficiency, and eliminating the requirement for human and animal participants. This method creates a framework for evaluating the efficacy of potential treatments against specific molecular targets, allowing for the prediction of their efficacy based on the structural properties of compounds before synthesis for subsequent in vitro and in vivo testing. Targeting the NF-kB protein is critical because it plays a role in many disorders involving immunological and inflammatory responses, stress responses, cellular proliferation, and apoptosis. These findings are essential for guiding future research into the role of the NF-kB protein in human disorders and identifying possible therapeutic targets.
References
Ali A, Shah FA, Zeb A, Malik I, Alvi AM, Alkury LT, Rashid S, Hussain I, Ullah N, Khan AU, Koh PO (2020) NF-κB inhibitors attenuate MCAO induced neurodegeneration and oxidative stress—a reprofiling approach. Frontiers in molecular neuroscience 13:33
https://doi.org/10.3389/fnmol.2020.00033
Barnabei L, Laplantine E, Mbongo W, Rieux-Laucat F, Weil R (2021) NF-κB: at the borders of autoimmunity and inflammation. Frontiers in Immunology 3169
https://doi.org/10.3389/fimmu.2021.716469
Begalli F, Bennett J, Capece D, Verzella D, D'Andrea D, Tornatore L, Franzoso G (2017) Unlocking the NF-κB Conundrum: Embracing Complexity to Achieve Specificity. Biomedicines 5(3):50
https://doi.org/10.3390/biomedicines5030050
Bonizzi G, Bebien M, Otero DC, Johnson-Vroom KE, Cao Y, Vu D, Jegga AG, Aronow BJ, Ghosh G, Rickert RC, Karin M (2004) Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimers. The EMBO journal 23(21):4202–4210
https://doi.org/10.1038/sj.emboj.7600391
Brasier AR (2010) The nuclear factor-kappaB-interleukin-6 signalling pathway mediating vascular inflammation. Cardiovasc Res 86(2):211-218
https://doi.org/10.1093/cvr/cvq076
Faes S, Dormond O. (2015) PI3K and AKT: unfaithful partners in cancer. International journal of molecular sciences. 16(9):21138-52.
Hayden MS, West AP, Ghosh S (2006) NF-kB and the immune response. Oncogene 25(51): 6758–80.
https://doi.org/10.3390/ijms160921138
Deptala A, Bedner E, Gorczyca W, Darzynkiewicz Z (1998) Activation of nuclear factor kappa B (NF-kappa B) assayed by laser scanning cytometry (LSC). Cytometry 33(3):376-382
https://doi.org/10.1002/(SICI)1097-0320(19981101)33:3<376::AID-CYTO13>3.0.CO;2-Q
Gilmore TD, Herscovitch M (2006) Inhibitors of NF-kappaB signaling: 785 and counting. Oncogene 25(51):6887-99
https://doi.org/10.1038/sj.onc.1209982
Hikmaranti M, Astiyani AM, Hasanah KM, Maghfiroh NM (2020) A Comparative Study of Gallic Acid, Ellagic Acid, Urolithin A, and Urolithin B with NF-κB Protein as Anti Type 2 Diabetes Mellitusby In Silico. JSMARTech: Journal of Smart Bioprospecting and Technology 1(2):031-5
https://doi.org/10.21776/ub.jsmartech.2020.001.02.2
Hira S, Saleem U, Anwar F, Raza Z, Rehman AU, Ahmad B (2020) In silico study and pharmacological evaluation of Eplerinone as an Anti-Alzheimer's drug in STZ-induced Alzheimer's disease model. ACS omega 5(23):13973-83
https://doi.org/10.1021/acsomega.0c01381
Jiang H, Fang J, Xing J, Wang L, Wang Q, Wang Y, Li Z, Liu R (2019) Tilianin mediates neuroprotection against ischemic injury by attenuating CaMKII-dependent mitochondrion-mediated apoptosis and MAPK/NF-κB signaling. Life sciences 216:233-45
https://doi.org/10.1016/j.lfs.2018.11.035
Jin M, Duan J, Liu W, Ji J, Liu B, Zhang M (2021) Feedback activation of NF-KB signaling leads to adaptive resistance to EZH2 inhibitors in prostate cancer cells. Cancer cell international 21(1):1-0
https://doi.org/10.1186/s12935-021-01897-w
Kaltschmidt B, Helweg LP, Greiner JF, Kaltschmidt C (2022) NF-κB in neurodegenerative diseases:Recent evidence from human genetics. Frontiers in Molecular Neuroscience 397 https://doi.org/10.3389/fnmol.2022.954541
Kanan T, Kanan D, Al Shardoub EJ, Durdagi S (2021) Transcription factor NF-κB as target for SARS-CoV-2 drug discovery efforts using inflammation-based QSAR screening model. J MolGraph Model 108:107968
https://doi.org/10.1016/j.jmgm.2021.107968
Latawa P, Chrisman BA (2021) Computational Modeling Framework to Analyse Synovial-TissueBased Drug Targets and Diagnostic Biomarkers in Rheumatoid Arthritis. bioRxiv https://doi.org/10.1101/2021.11.08.467813
Li WY, Yang F, Chen JH, Ren GF (2021) β-Caryophyllene Ameliorates MSU-Induced Gouty Arthritis and Inflammation Through Inhibiting NLRP3 and NF-κB Signal Pathway: In Silico and In Vivo. Front Pharmacol 12:651305https://doi.org/10.3389/fphar.2021.651305
Liu T, Zhang L, Joo D, Sun SC (2017) NF-κB signaling in inflammation. Signal Transduct Target Ther 2:17023 https://doi.org/10.1038/sigtrans.2017.23
Murwanti R, Kholifah E, Sudarmanto BA, Hermawan A (2020) Effect of curcumin on NF-κB P105/50 expression on triple-negative breast cancer (TNBC) and its possible mechanism of action. AIP Conference Proceedings 2260:040024https://doi.org/10.1063/5.0016423
Nandeesh R, Vijayakumar S, Munnolli A, Alreddy A, Veerapur VP, Chandramohan V, Manjunatha E(2018) Bioactive phenolic fraction of Citrus maxima abate lipopolysaccharide-induced sickness behaviour and anorexia in mice: In-silico molecular docking and dynamic studies of biomarkers against NF-κB. Biomedicine & Pharmacotherapy 108:1535-45 https://doi.org/10.1016/j.biopha.2018.10.004
Shankar E, Weis MC, Avva J, Shukla S, Shukla M, Sreenath SN, Gupta S. (2019) Complex Systems Biology Approach in Connecting PI3K-Akt and NF-κB Pathways in Prostate Cancer. Cells. 8(3):201 https://doi.org/10.3390/cells8030201
Siebenlist U, Franzoso G, Brown K (1994) Structure, regulation and function of NF-kappaB. Annual review of cell biology 10(1):405-55 https://doi.org/10.1146/annurev.cb.10.110194.002201
Singh H, Sen R, Baltimore D, Sharp PA (1986) A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes. Nature 319(6049):154-158 https://doi.org/10.1038/319154a0
Solt LA, May MJ (2008) The IkappaB kinase complex: master regulator of NF-kappaB signaling. Immunol Res 42(1-3):3-18 https://doi.org/10.1007/s12026-008-8025-1
Sung MH, Simon R (2004) In silico simulation of inhibitor drug effects on nuclear factor-kappaB pathway dynamics. Mol Pharmacol 66(1):70-5 https://doi.org/10.1124/mol.66.1.70
Uddin MZ, Paul A, Rakib A, Sami SA, Mahmud S, Rana MS, Hossain S, Tareq AM, Dutta M, Emran TB, Simal-Gandara J. (2021) Chemical profiles and pharmacological properties with in silico studies on elatostema papillosum wedd. Molecules 26(4):809 https://doi.org/10.3390/molecules26040809
Wu ZH, Miyamoto S (2007) Many faces of NF-kappaB signaling induced by genotoxic stress. J Mol Med (Berl) 85(11):1187-1202
https://doi.org/10.1007/s00109-007-0227-9
Yu H, Lin L, Zhang Z, Zhang H, Hu H (2020) Targeting NF-κB pathway for the therapy of diseases:mechanism and clinical study. Signal Transduct Target Ther 5(1):209
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